THE PULMONARYABNORMALITIES IN MYXEDEMA* t

By WILLIAM R. WILSONANDGEORGEN. BEDELL

(From the Pulmonary Laboratory of the Cardiovascular Research Laboratories, Department ofInternal Medicine, College of Medicine, State University of Iowa, Iowa City, Ia.)

(Submitted for publication July 14, 1959; accepted September 4, 1959)

The purpose of this paper is to report a studyof lung function in patients with myxedema. Re-cently we studied 28 obese persons and found 10who had alveolar hypoventilation manifested byincreased arterial Pco2 (2). They had either lungdisease or myxedema in association with theirobesity. The nature of pulmonary involvementin patients with myxedema has not been studied.Why did patients with obesity and myxedema de-velop alveolar hypoventilation? We postulatedthat patients with myxedema might have one orall of the following: a depression of the respiratorycenter in the brain, interference with neural con-duction or with neuromuscular transmission to therespiratory muscles, disease of the respiratorymuscles, or a change in the character of the alveo-lar capillary membrane.

The existence of central nervous system abnor-malities in myxedema is known. In 1904, Gull(3) included myxedema under "Diseases of theNervous System" in a collection of his writings.Scheinberg, Stead, Brannon and Warren (4)measured cerebral blood flow in eight patientswith myxedema by the nitrous oxide techniqueand found that the average cerebral blood flow was38 per cent below normal, oxygen and glucoseconsumption 27 per cent below normal, and cere-bral vascular resistance 91 per cent above normal.Browning, Atkins and Weiner (5) found en-cephalographic changes in seven psychotic adultswith myxedema. The electroencephalogram re-turned toward normal as the patient's myxedemaimproved. These are a few of the many studies

* Presented in part at the midwestern section meetingof the American Federation for Clinical Research inChicago, Ill., October 30, 1958 (1), and at the annualmeeting of The American Goiter Association in Chicago,Ill., April 30, 1959.

tSupported by a research grant from the Iowa Tu-berculosis and Health Association, and aided by grantsfrom the National Heart Institute of the United StatesPublic Health Service (H-3304) and the Iowa HeartAssociation.

which indicate that central nervous system in-volvement exists in myxedema. It is reasonableto postulate that the respiratory center could beinvolved.

The fact that there are lesions in the musclesand perhaps changes in neural conduction orneuromuscular transmission to the muscles is es-tablished. Pathologic studies have demonstrated amucoid substance in skin, subcutaneous tissue,mucous membranes of the upper respiratory tract(6), and skeletal muscles (7-9) in severe myx-edema. Lambert, Underdahl, Beckett and Me-deros (10) believe the slow ankle jerk in myx-edema is caused by an abnormality of the con-tractile mechanism of the muscle rather than bychanges in the neural elements of the reflex or inthe mechanism of excitation of the muscle. Wald-stein, Bronsky, Schrifter and Oester (11) insertedneedle electrodes directly into the muscle of pa-tients with myxedema and found abnormal electro-myograms which reverted to normal after treat-ment of the patients with desiccated thyroid. In-gold (12) abolished the prolonged muscle con-traction and relaxation time in myxedematous ratsby blocking transmission at the neuromuscularjunction with curare. Whether the primary lesioninvolves the muscle, neural conduction, or neuro-muscular transmission is beyond the scope of thispaper. "Muscular" involvement might be ex-pected to produce changes in the patient's abilityto ventilate his lungs.

Evidence of capillary involvement in myxedemais available. Zondek, Michael and Kaatz (13)studied the ungual limbus capillaries in six patientswith myxedema and found them to be reducedin number and size. After thyroid therapy thecapillaries were present in normal number and thecaliber of the vessels was normal. Lange (14)studied five patients with myxedema and founda large increase in capillary permeability whichreturned to normal following treatment of themyxedema. In autopsy material, Baker and Ham-

42

PULMONARYABNORMALITIES IN MYXEDEMA

ilton (15) found thickening of the walls of thecapillaries of the heart in myxedema. Foster andBarr (7) found slight but definite fibrous thicken-ing of the alveolar walls of a patient who died withsevere myxedema. It is reasonable to postulatesimilar lesions in the pulmonary capillaries whichmight cause reduction in the diffusing capacity ofthe lungs.

This paper reports studies of pulmonary func-tion in 26 patients with myxedema before treat-ment. Twenty-one were studied again after treat-ment with desiccated thyroid or triiodothyronine.

METHODS

The patients were selected from the wards and clinicsof the University Hospitals and Veterans Administra-tion Hospital, Iowa City. Each patient had a completehistory, physical examination, roentgenogram of thechest, thyroid function studies and other indicated labora-tory tests. The diagnosis of myxedema was based oncharacteristic history, physical findings and laboratoryfindings. Werequired that the protein-bound iodine de-termination be below 3.0 fig. per 100 ml. of plasma (therange of normal values in the biochemistry laboratory,University Hospitals, is 3.5 to 8.0 Ag. per 100 ml. ofplasma); and that the radioactive iodine uptake at 24hours be less than 10 per cent (the range of normal val-ues in the radiation laboratory, University Hospitals, is15 to 45 per cent). Pulmonary disease was excluded ifthe patient had no symptoms of lung disease, no physi-cal findings of lung disease, and a normal roentgenogramof the chest. The basal metabolic rate was measured bystandard techniques using the Sanborn basal metabolismapparatus. The protein-bound iodine determinationswere performed by a slight modification of Barker,Humphrey and Soley's method (16). The 24 hour uptakeof radioactive iodine was measured in the Radiation Re-search Laboratory by the method of Evans (17). Thefasting total serum cholesterol was determined by themethod of Pearson, Stern and McGavack (18). Thy-roid stimulating hormone (TSH) stimulation tests weredone when indicated to help differentiate primary fromsecondary myxedema. Pulmonary function tests andarterial blood studies were done in the morning after thepatient had eaten breakfast, according to methods previ-ously described from this laboratory (2). Predicted nor-mal values for vital capacity were calculated on the basisof the patient's height (19). Predicted normal valuesfor inspiratory capacity are 75 per cent of predicted vitalcapacity; predicted normal values for expiratory reservevolume are 25 per cent of predicted vital capacity. Pre-dicted normal values for total lung capacity were calcu-lated as follows: for patients 15 to 34 years in age, thepredicted vital capacity divided by 0.80 (20); for pa-tients 35 to 50 years in age, the predicted vital capacitydivided by 0.766 (20); and for patients over 50 years in

age, the predicted vital capacity plus 2,430 ml. (21).The predicted normal values for the maximal breathingcapacity (MBC) were the mean values found by Bald-win, Cournand and Richards (22) taking into considera-tion sex and age of the subject but not body surface area.The predicted normal values for the diffusing capacityof the lung for carbon monoxide (DLoo) were based onthe regression equation of Ogilvie, Forster, Blakemoreand Morton (23) which is DLao= height (in inches) X0.874 - 31.6.

Six of our patients were extremely obese and hadmyxedema. After the initial studies were completed, thesewere given an 800 calorie diet and desiccated thyroid ortriiodothyronine. When possible, patients were hos-pitalized until they were nearly euthyroid and had lost50 to 100 pounds. Sometimes this took six months.Four patients had clinical evidence of lung disease inaddition to myxedema.

The remaining 16 patients had myxedema, but noclinical evidence of lung disease. These patients wereusually hospitalized for "initial" pulmonary studies andthe initiation of thyroid therapy. Then they were seenat three month intervals in the medical out-patient de-partment. At the return visit, each patient had an in-terval history, physical examination and the necessarythyroid function tests. Most of the patients in this groupwere judged to be euthyroid or nearly so by the time ofthe last study.

Statistical analysis of the data was done using the testof significant difference in paired data by the methodof Fisher (24). The formula used was:

t(n-l) =

\2f (d d)2n (n -1)

where a = the difference between the means, 2 (d-d)= sum of the squares of the individual differences minusthe difference between the means and n = number of pa-tients studied.

The patients are divided into two groups. Sixteen pa-tients had myxedema but no evidence of lung disease andare considered in Group I. Patients in Group II hadmyxedema and either (A) were obese (six patients) or (B)had lung disease (four patients).

RESULTS

A. Patients with myxedema but no clinical lungdisease

This group consists of 16 patients whose agerange was 26 to 68 years. There were 6 men and10 women. The average weight of the group was161 pounds. The results of thyroid function stud-ies in these patients are listed in Table I. Themean basal metabolic rate was minus 27; meanprotein-bound iodine was 2.0 pg. per 100 ml. ofplasma; mean 24 hour radioactive iodine uptakewas 3.3 per cent; mean total cholesterol was 399

43

WILLIAM R. WILSONANDGEORGEN. BEDELL

mg. per 100 ml. of serum. The type of myxedema,the duration of symptoms and the daily dose ofdesiccated thyroid or triiodothyronine are shownin Table I. All but one of the patients (M. M.)were studied before thyroid treatment was started.The results of pulmonary function studies in thesepatients are listed in Tables II and III. The lungvolumes were normal. Distribution of inspired airwas slightly uneven in six patients as measuredby the single breath nitrogen test, but normal asmeasured by the less sensitive test based on theper cent of nitrogen at the end of seven minutesof oxygen breathing. There were slight abnor-malities in the mechanical tests. The mean maxi-mal breathing capacity was 82 per cent of predictednormal. The maximal expiratory flow rate av-eraged 224 L. per minute while the maximal in-spiratory flow rate averaged 154 L. per minute.The mean DL0C was definitely reduced, being 68per cent of predicted normal.

Thirteen patients in this group were studiedafter approaching or reaching the euthyroid state.The diuresis produced by therapy caused a sig-nificant mean weight loss of 14 pounds (p < 0.01).The mean basal metabolic rate increased signifi-cantly from - 28 to - 8 (p < 0.01); the meanprotein-bound iodine increased significantly from1.9 to 5.9 pg. per 100 ml. of plasma (p < 0.01);while the total cholesterol decreased significantlyfrom 431 to 249 mg. per 100 ml. of serum (p <0.001). Treatment did not alter the lung volumessignificantly. Mean alveolar ventilation increasedslightly from 4.0 to 4.6 L. (p > 0.2). In re-sponse to breathing 7.5 per cent CO2 in air, themean minute volume of ventilation in these 10 pa-tients increased from 18.7 to 21.6 L. (p > 0.3).Alveolar gas distribution as measured by the singlebreath nitrogen test did not change significantly(p > 0.9). The maximal breathing capacity in-creased significantly from a mean of 78 to 102 percent of predicted normal (p = < 0.01). Themean expiratory flow rate was 213 L. per minutebefore thyroid replacement and 250 L. per minuteafterward (p > 0.1). The maximal inspiratoryflow rate increased from a mean of 152 to 167L. per minute (p > 0.4). The DL00 in 12 pa-tients increased significantly from a mean of 69to a mean of 93 per cent of predicted normal(p < 0.01).

The results of arterial blood studies in these pa-tients are listed in Table IV. Mean arterial oxy-gen saturation at rest was 97 per cent, mean pCO2was 39 mm. Hg, mean pH was 7.41, and the meanhematocrit was 35 per cent. Thyroid administra-tion to these patients produced no significantchanges except that the mean hematocrit increasedfrom 35 to 40 per cent (p = < 0.05).

B. Patients with myxedema and obesityThis group is composed of six patients, five

women and one man, with myxedema, whose meanweight was 294 pounds. Their ages ranged from41 to 67 years. The initials, physical character-istics, results of thyroid function tests, type ofmyxedema, duration of symptoms and daily doseof thyroid in these patients are listed in Table V.The mean basal metabolic rate was minus 17; themean protein-bound iodine was 1.6 pg. per 100 ml.of serum; the mean 24 hour uptake of radioactiveiodine was 2.8 per cent; the mean total cholesterolwas 461 mg. per 100 ml. of serum. Five had pri-mary myxedema and one had myxedema followingradioactive iodine therapy for thyrotoxicosis. Theaverage duration of symptoms in this group was8.5 years. Two of the patients (H. K. and E. K.)received small doses of desiccated thyroid beforethe initial studies were done. Four patients wererestudied after treatment with a reducing diet anddesiccated thyroid or triiodothyronine. The meaninitial weight in these four patients was 292 poundsand at the time of last study it was 223 pounds, amean loss of 69 pounds.

The results of lung volume studies in thesepatients are listed in the top half of Table VI. Ini-tially, the lung volumes were reduced. Mean in-spiratory capacity was 76 per cent of predictednormal; mean expiratory reserve volume was 64per cent of predicted normal; mean vital capacitywas 71 per cent of predicted normal and mean totallung capacity was 66 per cent of predicted normal.In the four patients studied after therapy, the lungvolumes returned to or toward normal.

In the top half of Table VII, the results of ven-tilatory studies, respiratory mechanics and diffu-sion are listed. Initially, in these six patients withmyxedema and obesity, the mean minute volumeof ventilation was 6.4 L. and the mean alveolarventilation was 2.9 L. The mean maximal breath-

44

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TABLE IV

Arterial blood studies in patients with myxedema but no lung disease

02 02 saturationDate of content 02 pC02 pH Hem-

Patient study (rest) capacity Rest 100% 02* (rest) (rest) atocrit

V. C. 20 June 5815 Sept. 58

L. A. 23 June 5823 Dec. 58

R. T. 27 June 588 Oct. 58

M. Mc. 23 Jan. 587 Oct. 58

H. H. 18 Sept. 5819 Feb. 59

M. M. 10 Dec. 57W. P. 16 Dec. 57

23 Apr. 581 Oct. 58

10 Dec. 58M. R. 27 May 58

30 Sept. 58A. C. 14July 58

18 Feb. 59G.D. 17July 58

7 Jan. 59W. R. 14 Mar. 58

7 Jan. 59A. F. 8 Oct. 57

22 Sept. 58Cl. P. 4 Dec. 57

18 Feb. 58C. P. 3 Mar. 58L. M. 11 Sept. 58E. D. 4 Mar. 59

Vol. %13.3015.3413.5913.9610.0314.7815.3517.4514.95

14.946.457.39

17.6416.4611.99

16.5916.2415.8315.7013.7617.2213.2315.0415.1515.7511.0216.3910.43

Vol. %13.6115.8813.0415.2710.3114.6915.3018.0915.65

15.386.877.33

17.6216.4412.47

16.1916.0615.1315.8914.1216.3913.6514.5915.9616.2510.1917.7111.31

Mean (initial) 16 patientsMean (before treatment) 10 patientsMean (after treatment) 10 patients

97.796.6

100 + 0.391.497.3

100 + 0.1100 + 0.1

96.595.5

97.193.9

100 + 0.1100 + 0.02100 + 0.02

96.2

100 + 0.4100 + 0.2100 + 0.7

98.897.599.096.9

100 + 0.594.996.9

100 + 0.894.192.2

97.197.897.9

100 + 1.71100 + 1.99100 + 2.69100 + 1.20100 + 1.94100 + 1.86100 + 2.21100 + 1.71100 + 1.76

100 + 3.14100 + 1.21100 + 1.87100 + 1.98100 + 2.14

100 + 2.23100 + 1.94100 + 2.48100 + 2.30100 + 1.61100 + 1.98100 + 1.58100 + 1.87100 + 1.28100 + 1.33100 + 2.42100 + 1.27100 + 1.65

mm. Hg384044414140413640

7.437.377.387.407.427.417.337.417.41

46 .7.3545 7.3836 7.4434 7.4538 7.4335 7.50

32 7.4533 7.4835 7.4336 7.4236 7.4037 7.4140 7.3836 7.3944 7.4237 7.3239 7.3334 7.4536 7.46

333936383037414537443820244443303540404043333940373838294231

39 7.41 3540 7.40 35t37 7.40 40t

* Values following + sign refer to milliliters of 02 per 100 ml. blood in excess of that required to saturate hemoglobin(i.e., dissolved 02). Normal value for dissolved 02 is 2.00 ml.

t Mean value represents 12 patients.

ing capacity was 68 per cent of predicted normal.The maximal expiratory flow rate averaged 135 L.per minute while the mean inspiratory flow ratewas 101 L. per minute. The mean DLro was low,being only 60 per cent of predicted normal. Inthe four patients studied after therapy, the mean

minute volume of ventilation increased from 5.9to 8.9 L. and the mean alveolar ventilation in-creased from 2.9 to 5.5 L. The mean maximalbreathing capacity increased from 73 to 114 percent of predicted normal. The mean maximal ex-

piratory flow rate increased from 125 to 275 L. per

minute and the mean inspiratory flow rate in-creased from 90 to 182 L. per minute. TheDi.co increased from 14 to 22 ml. CO per mm.Hg per minute (or from 57 to 88 per cent of pre-dicted normal).

The results of arterial blood studies in these pa-tients are shown in the top part of Table VIII.Pulmonary insufficiency for oxygenation and car-bon dioxide elimination was present in five of thesix patients. The mean arterial oxygen satura-tion was 84 per cent; the mean pCO2 was 55 mm.Hg and the mean pH was 7.35. The mean hemato-

48

PULMONARYABNORMALITIES IN MYXEDEMA

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crit was 43 per cent. Four patients were studiedafter treatment. The mean arterial oxygen satu-ration increased from 80 to 93 per cent; the meanpCO, decreased from 61 to 40 mm. Hg and thepH increased from 7.32 to 7.40. The mean he-matocrit decreased from 44 to 40 per cent.

C. Patients with myxedema and clinical lungdiseaseThis group consists of four patients with myx-

edema and clinical lung disease. One woman hadpneumonia; two women had pulmonary edemasecondary to heart disease and one man had pul-monary emphysema. The results of pulmonaryfunction studies and arterial blood studies in thesepatients are listed in the lower half of Tables VI,VII and VIII.

DISCUSSION

Lung volumes

In contrast to previous investigators (25, 26),we found the vital capacity was essentially normalin 16 patients with uncomplicated myxedema, re-

gardless of the cause. Our results are similar tothose obtained by Schnitker, Van Raalte and Cutler(27). In patients with angina pectoris they in-duced myxedema by total thyroidectomy. Theirpatients had a normal vital capacity after induc-tion of myxedema. Our patients with myxedemaand obesity had moderate reduction in inspiratorycapacity, expiratory reserve volume, vital capacity,residual volume and total lung capacity. Obesepatients without myxedema or lung disease havereduced lung volumes (2). Wethink that whenthe two diseases coexist the reduced lung volumesare secondary to obesity. When the obese pa-

tients lost weight, their lung volumes returned tonormal (Table VI).

Ventilation

Patients with myxedema alone ventilated ade-quately as measured by minute volume of ventila-tion, arterial pCO2 and arterial 02 saturation.They had a lower minute volume of ventilationfollowing the stimulus of breathing 7.5 per centcarbon dioxide in air than did a group of normals.In the normals, the mean minute volume duringthe third minute of carbon dioxide breathing was

31.2 L. as compared to 17.8 L. for the 16 patients

with myxedema alone. Whether this diminishedresponse represents primary depression of therespiratory center in the brain or inability of thechest bellows to respond adequately to the stimu-lus is unknown. Treatment of the myxedema re-sulted in a small but not significant increase in theminute volume of ventilation of these patients inresponse to breathing 7.5 per cent carbon dioxidein air.

Four of the six patients with myxedema andobesity had alveolar hypoventilation manifested byincreased arterial pCO2 and low alveolar ventila-tion. The existence of alveolar hypoventilationin any patient must be caused by lung disease,malfunction of the chest bellows, inadequate neuro-muscular coordination, or a central nervous systemlesion. The physiologic problem is to identifywhich of these four causes the derangement of thefunction. Lung disease and disease of the bonythorax are excluded in these patients. The troublemust be either in the respiratory center in thebrain, the muscles of respiration, or neuromuscularcoordination singly or in combination. Wehaveno proof of what comes first or of how manymechanisms are involved. We suspect that themuscles of respiration and neuromuscular coordi-nation are impaired. The evidence which favorsthis is that patients with myxedema alone do havea significantly reduced maximal breathing ca-pacity. The added burden of obesity results infurther reduction in maximal breathing capacityand slowing of both expiratory and inspiratoryflow rates. The process is reversible becausetreatment of the patients with myxedema andobesity resulted in restoration of normal alveolarventilation in most patients. This took placegradually and over a period of several months asillustrated by L. R., H. K. and B. B. (Tables Vthrough VIII).

Mechanics of breathing

The patients with myxedema alone had reducedmaximal breathing capacity which increased sig-nificantly following therapy. The ability of a pa-tient to perform this test well is dependent on thecooperation of the patient, the force of the respira-tory muscles, and the patency of the respiratoryairways. Wedid not measure airway resistance.We believe the patients were cooperative. We

51

WILLIAM R. WILSONANDGEORGEN. BEDELL

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TABLE VIII

Arterial blood studies in: A. patients with myxedema and obesity; B. patients with myxedema and lung disease

02 02 saturationDate of content 02 pC02 pH Hema-

Patient study (rest) capacity Rest 100% 02* (rest) (rest) tocrit

Vo % Vol. % % % mm. Hg %

A. Patients with myxedema and obesityL. R. 14 Mar. 57 12.34 15.01 82.2 100 + 1.70 54 7.31 41

4 June 57 13.35 14.82 90.1 100 + 1.50 42 7.37 3821 Nov. 57 13.96 14.64 95.4 42 7.36 37

7 Apr. 58 14.39 14.94 96.3 100 + 2.09 36 7.42 379 Oct. 58 14.50 15.28 94.9 100 + 1.34 33 7.42 36

H. K. 22 Jan. 58 14.35 18.03 79.6 100 + 0.62 60 7.35 4414 Feb. 58 14.67 17.47 84.0 100 + 0.30 48 7.39 43

6 Mar. 58 14.79 17.35 85.2 100 + 1.09 51 7.37 4215 Apr. 58 16.02 18.15 89.9 100 + 0.94 49 7.36 4515 Apr. 58t 17.81 18.19 97.9 45 7.37 45

3 Sept. 58 15.96 16.86 94.7 100 + 1.39 43 7.40 43.B. B. 18 Sept. 58 11.74 15.89 73.9 98.5 82 7.27 44

14 Oct. 58 12.82 16.88 75.6 94.4 76 7.29 384 Nov. 58 14.22 16.32 87.1 100 + 1.37 63 7.35 43

25 Feb. 59 14.68 15.71 93.4 100 + 1.23 38 7.46 39E. K. 12 Sept. 58 16.44 19.58 84.0 100 + 0.42 46 7.37 47

21 Jan. 59 15.34 17.61 87.1 100 + 1.30 44 7.36 43K. P. 3 Sept. 57 12.99 14.33 90.6 100 + 0.75 49 7.34 37Mar. R. 25 Sept. 58 15.99 17.60 90.9 100 + 1.17 38 7.43 42

Mean (initial) 6 patients 83.5 55 7.35 43Mean (before treatment) 4 patients 79.9 61 7.32 44Mean (after treatment) 4 patients 92.5 40 7.41 40

B. Patients with myxedema and lung diseaseB. W. 20 Nov. 57 9.48 9.35 100 + 0.1 100 + 3.15 40 7.38 26M. Mar. 9 Apr. 58 21.83 22.78 95.8 100 + 1.98 36 7.44 57A. L. 24 June 58 13.30 13.88 95.8 100 + 0.91 36 7.45 36W. H. 30 June 58 15.82 16.18 97.8 100 + 1.58 30 7.46 40

* Values following + sign refer to milliliters 02 per 100 ml. blood in excess of that required to saturate hemoglobin(i.e., dissolved 02). Normal value for dissolved O2 is 2.00 ml.

t Arterial studies done with patient in sitting position.

suspect that the change in the maximal breathingcapacity is caused by changes in the respiratorymuscles. We have no evidence to demonstratewhether this is an abnormality in the contractilemechanism of the muscles as postulated by Lam-bert and co-workers (10) or in the neural con-duction or neuromuscular transmission. Treat-ment of the patients with myxedema alone andthose with myxedema and obesity resulted in areturn of the mechanical tests to or toward nor-mal, suggesting that the "muscular" lesion isreversible.

DiffusionPatients with myxedema and no lung disease

had a diminished DLCO which improved signifi-cantly after thyroid therapy. The DL0O depends

on several factors: 1) the capillary surface avail-able for diffusion, 2) the thickness of the alveolarcapillary membrane and 3) the total amount ofhemoglobin in pulmonary capillary blood and thereaction rate of hemoglobin with carbon monoxide.All three of these factors may be altered in myx-edema. The work of Zondek and associates (13),Lange (14), and Baker and Hamilton (15) sug-gests that the capillaries might be reduced in num-ber and size, and that there might be alterations inthe walls of the capillaries. Circulating plasmaand total blood volumes are diminished in myx-edema (28-30). Therefore it is possible that pul-monary capillary blood volume is reduced. In our13 patients with myxedema and no lung diseasestudied before and after therapy, the mean hemato-crit increased significantly from 35 to 40 per cent(p = < 0.05). The Drco increased significantly

53

WILLIAM R. WILSON AND GEORGEN. BEDELL

TABLE IX

DLCO, hemoglobin and hematocrit in Patient E. D. before andafter transfusion with washed red blood cells

WashedHemo- Hema- red blood

Date DLO0 globin tocrit cells

ml. CO/ Gm./100 %mm.Hg/min. ml.

11 Mar. 59 10 9.3 31 500 cc.12 Mar. 59 10 10.7 3313Mar.59 11 10.8 35 500 cc.16 Mar. 59 11 11.9 37 500 cc.17Mar.59 10 12.5 3918Mar.59 11 12.8 4019 Mar. 59 9 12.3 41 500 cc.20 Mar. 59 9 12.4 4521 Mar. 59 9 13.2 4323 Mar. 59 11 13.2 43

from 69 to 93 per cent of predicted normal (p =< 0.01). Rankin, McNeill, and Forster (31)found DLCO reduced in patients with anemia.In our patients the improvement in the hematocritparallels the improvement in DLCO, especially inPatients W. P. and W. R. However, DLCo in-creased with little change in hematocrit in PatientsM. Mc. and A. F. Patient E. D., who had myx-edema, anemia and a low DILco, was studied in aneffort to clarify this point. His other pulmonaryfunction tests were essentially normal. Whilestill frankly myxedematous his hematocrit waselevated from 30 to 44 per cent by transfusions ofwashed red blood cells; at the same time DLCo re-mained essentially unchanged (Table IX). Thissuggests that there is significant reduction in DLCOwhich is on the basis of capillary changes in thelungs. This suggestion is supported by the stud-ies of DLCO in patients with myxedema andobesity. Patients with obesity alone have a nor-mal DLCO (2). The four patients with myxedemaand obesity had a low DLCOand a normal hemato-crit before thyroid therapy and a normal DLcoand slight fall in hematocrit after therapy. Wesuspect that myxedema produced changes in thecapillaries of the lung which result in a loweredDLo. Wedo not know if this is a reduction inthe total number of capillaries involved in diffu-sion, a thickening of the alveolar capillary mem-brane, or both.

SUMMARYAND CONCLUSIONS

We have studied 26 patients with myxedemabefore treatment and restudied 21 after treatment

with desiccated thyroid or triiodothyronine. Six-teen patients had myxedema but no evidence oflung disease, six patients had myxedema and wereobese, four patients had myxedema and lungdisease.

The lung volumes were normal in the patientswith myxedema only. Obese patients with myx-edema had moderate reduction in inspiratory ca-pacity, expiratory reserve volume, vital capacity,residual volume and total lung capacity, probablyon the basis of obesity. When the obese patientslost weight their lung volumes returned to normal.

Four of six patients with myxedema and obesityhad alveolar hypoventilation. The precise mecha-nism of alveolar hypoventilation is unknown.Lung disease and disease of the bony thorax wereabsent. This leaves the possibility of malfunctionof the respiratory center in the brain, the musclesof respiration or neuromuscular coordination.We suspect that the muscles of respiration orneuromuscular coordination are involved. Themaximal breathing capacity was reduced in pa-tients with myxedema and increased significantlyafter therapy. This suggests that there is a"muscular" lesion which is reversible.

The diffusing capacity of the lungs for carbonmonoxide (Drco) is reduced in patients with myx-edema and increases slowly but significantly aftertherapy. The best explanation for this is pul-monary capillary involvement, either a thickenedalveolar capillary membrane or a reduction in thepulmonary capillary bed, or both.

ACKNOWLEDGMENTS

The authors acknowledge the technical help of Mrs.Jeannette Messerli, Mrs. Marjorie Guirl, Mrs. Irene Buch-man, Mrs. Mary Ann Chamberlain, Mrs. Arlene Cohen,Mr. Donald Laughlin and Mr. Robert Clark. We areindebted to Dr. John Eckstein, Dr. Walter Kirkendalland Dr. William Bean for critical review of the work andto Mrs. Vonnie Tweed and Mrs. Nancee Blum for prepa-ration of the manuscript.

REFERENCES1. Wilson, W. R., and Bedell, G. N. The pulmonary

abnormalities in myxedema (abstract). Clin. Res.1958, 6, 420.

2. Bedell, G. N., Wilson, W. R., and Seebohm, P. M.Pulmonary function in obese persons. J. clin. In-vest. 1958, 37, 1049.

3. Gull, W. W. A Collection of the Published Writings

54

PULMONARYABNORMALITIES IN MYXEDEMA

of William Wilhey Gull. London, New Syden-ham Society, 1894, vol. 1, pp. 315-321.

4. Scheinberg, P., Stead, E. A., Jr., Brannon, E. S., andWarren, J. V. Correlative observations on cere-bral metabolism and cardiac output in myxedema.J. clin. Invest. 1950, 29, 1139.

5. Browning, T. B., Atkins, R. W., and Weiner, H.Cerebral metabolic disturbances in hypothyroid-ism. Clinical and electroencephalographic studiesof the psychosis of myxedema and hypothyroidism.Arch. intern. Med. 1954, 93, 938.

6. Boyd, William. Pathology for the Physician. Phila-delphia, Lea and Febiger, 1958, p. 538.

7. Foster, M., and Barr, D. P. Myxedema: Record ofan autopsied case with special emphasis upon le-sions of muscles. J. clin. Endocr. 1944, 4, 417.

8. Means, J. H. The Thyroid and Its Diseases, 2nd ed.Philadelphia, J. 'B. Lippincott, 1948.

9. Anderson, W. A. D. Pathology. St. Louis, C. V.Mosby Co., 1948, p. 1065.

10. Lambert, E. H., Underdahl, L. O., Beckett, S., andMederos, L. 0. A study of the ankle jerk inmyxedema. J. clin. Endocr. 1951, 11, 1186.

11. Waldstein, S. S., Bronsky, D., Shrifter, H. B., andOester, Y. T. The electromyogram in myxedema.Arch. intern. Med. 1958, 101, 97.

12. Ingold, A. H. Tension Output in Hyperthyroid andHypothyroid Muscles Stimulated Directly and In-directly (thesis). Chicago, University of Illinois,1956.

13. Zondek, H., Michael, M., and Kaatz, A. Capillariesin myxedema. Amer. J. med. Sci. 1941, 202, 435.

14. Lange, K. Capillary permeability in myxedema.Amer. J. med. Sci. 1944, 208, 5.

15. Baker, S. M., and Hamilton, J. D. Capillary changesin myxedema. Lab. Invest. 1957, 6, 218.

16. Barker, S. B., Humphrey, M. J., and Soley, M. H.The clinical determination of protein-bound iodine.J. clin. Invest. 1951, 30, 55.

17. Evans, T. C. Radioactive iodine in the study ofthyroid disorders. J. Iowa St. med. Soc. 1955, 45,179.

18. Pearson, S., Stern, S., and McGavack, T. H. A rapidaccurate method for determination of total choles-terol in serum. Analyt. Chem. 1953, 25, 813.

19. West, H. F. Clinical studies on the respiration.VI. Comparison of various standards for the nor-mal vital capacity of the lungs. Arch. intern.Med. 1920, 25, 306.

20. Aslett, E. A., Hart, P. D., and McMichael, J. Lungvolume and its subdivisions in normal males.Proc. roy. Soc. B 1939, 126, 502.

21. Greifenstein, F. E., King, R. M., Latch, S. S., andComroe, J. H., Jr. Pulmonary function studiesin healthy men and women 50 years and older.J. appl. Physiol. 1952, 4, 641.

22. Baldwin, E. DeF., Cournand, A., and Richards,D. W., Jr. Pulmonary insufficiency. I. Physio-logic classification, clinical methods of analysis,standard values in normal subjects. Medicine(Baltimore) 1948, 27, 243.

23. Ogilvie, C. M., Forster, R. E., Blakemore, W. S.,and Morton, J. W. A standardized breath holdingtechnique for the clinical measurement of the dif-fusing capacity of the lung for carbon monoxide.J. clin. Invest. 1957, 36, 1.

24. Fisher, R. A. Statistical Methods for ResearchWorkers, 10th ed. Edinburgh, Oliver and Boyd,Ltd., 1946.

25. Blumgart, H. L., Gargill, S. L., and Gilligan, D. R.Studies on the* velocity of blood flow. XIV.The circulation in myxedema with a comparisonof the velocity of blood flow in myxedema andthyrotoxicosis. J. clin. Invest. 1930, 9, 91.

26. Hallock, P. The heart in myxedema, with a reportof 2 cases. Amer. Heart J. 1933, 9, 196.

27. Schnitker, M. T., Van Raalte, L. H., and Cutler,E. C. Effect of total thyroidectomy in man,Laboratory studies and observations of clinical ef-fects in thirty-nine cases. Arch. intern. Med. 1936,57, 857.

28. Thompson, W. 0. Studies in blood volume. I. Theblood volume in myxedema with a comparison ofplasma volume changes in myxedema and cardiacedema. J. clin. Invest. 1926, 2, 477.

29. Gibson, J. G., and Harris, A. W. Clinical studies ofthe blood volume. V. Hyperthyroidism and myx-edema. J. clin. Invest. 1939, 18, 59.

30. Ellis, L. B., Mebane, J. G., Maresh, G., Hultgren,H. N., and Bloomfield, R. A. The effect ofmyxedema on the cardiovascular system. Amer.Heart J. 1952, 43, 341.

31. Rankin, J., McNeill, R. S., and Forster, R. E. Dif-fusion characteristics of the pulmonary membraneand capillary bed in various diseases of the lungsand cardio-vascular system (abstract). J. clin.Invest. 1957, 36, 922.

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