View
1.899
Download
2
Tags:
Embed Size (px)
Citation preview
PROF.DR.G.SUNDARAMURTHY’S UNIT
DR.K.SENTHAMIZH SELVAN
A CASE OF HYPOGONADISM
CASE DETAILS
Balaji23 years Male kancheepuram
CLINICAL PRESENTATION
C/O delayed developmental milestones C/O diminished vision since childhood C/O poor development of genitalia
HISTORY OF PRESENT ILLNESS ----- patient had delay in attaining gross motor ,fine
motor,psycho-social and language milestones ----- From the age of 5 years patient had visual
disturbance ,which was progressive , not associated with
double vision,watering , pain or reddening of eyes patient had poor school performance and he was
a drop-out from 2 nd std. lost interest in games ,toys and surroundingsHe was not employed and did house hold
activities . At 22 years of age he presented with poorly
developed genitals no h/o penile erection,no early morning penile
tumescence , no h/o ejaculation
Had normal development of facial, pectoral, axillary and pubic hair .
No h/o seizures No h/o weakness of limbs H/o snoring + No h/o disturbances in sleep pattern. No h/o chest pain ,palpitation,
breathlessness No significant fever history
PERINATAL HISTORY: - no h/o drug intake by mother for any
ailments - no h/o fever or any other medical ailments
during pregnancy - born of normal ,vaginal delivery - no h/o prolonged labor - no h/o neonatal fever or seizures
FAMILY HISTORY : - Born of a 2 degree consanguinous marriage - other sibbling is normal - no other member in the family is having
similar complaints.
ON EXAMINATION
Patient was Conscious
Responding to oral commands
Afebrile
Hydration fair
Obese –BMI of 31kg/m^2 (ht =155 cms, wt=75 kg)
B/L gynaecomastia
Short neckShort neck
Ht : neck ratio of 14
Poly dactylyPoly dactyly
------ post axial
high arched palateFacial ,axillary and pectoral hairs are
present normally no pallor anicteric No cyanosis no clubbing no significant generalised lymphadenopathy no pitting pedal edema
Flat footFlat foot
BP: 110/80mmHg
Pulse: 84 /min ,regular
CVS: S1,S2 + nomurmur RS: NVBS + no added sounds P/A: soft,no HSM, BS+
GENITALIA: small sized penis, external urethral meatus normal, both testicles small sized – in the
scrotal sac pubic hair distribution –normal no varicocele
CNS : conscious responding to oral commands subnormal IQ divergent squint , vision – perception
of hand
movements pupils equally reacting to light
Optic fundus
Optic fundus
Ophthal opinion
media clear disc pallor bony spicules like structures consistent with
----RETINITIS PIGMENTOSA
ENT EVALUATION
--- B/L mild sensorineural hearing loss
No other cranial nerve involvement
motor system-N
sensory system-N
no cerebellar signs
no meningeal signs
problems
developmental delay learning disability strabismus retinitis pigmentosa mild sensorineural hearing loss obesity poly dactyly hypogonadism
INVESTIGATIONS
Urine: alb-nil sug –nil dep-1-2 pus cells CBC: Hb-10.4gms% TC-6400cells/cumm DC-P60/L38/E2 ESR-4/10mm RFT: blood sugar-110mgs% urea-38mgs% serum creatinine-0.9mgs% serum Na-144meq/dl K-4.8meq/dl
LFT:T.bilirubin- 1.2mg/dl direct-0.6mg/dl SGOT-44IU/L SGPT-86IU/L SAP-108IU/L T.protein-5.5gms/dl s.albumin-3.8gms/dl s.globulin-1.9gms/dl
LIPID PROFILE: s.total cholesterol- 210mgs/dl LDL-170mgs/dl HDL-40mgs/dl TGS-140mgs/dl
ECG- WNL
CHEST XRAY-NORMAL STUDY
ECHO : Normal study USG ABDOMEN : liver : 13.5 cm,spleen: 11.5 cms RK: 10.4×6.6cm LK: 9.3×4.8cm pancreas: normalUSG SCROTUM:Rt. Testis: 3×1.7×1.3cm
parenchyma Lt.testis: 3×2.1×1.6cm
normal cord,epididymis: normal tunica sac: normal
MRI BRAIN
IMPRESSION
----partially empty sella with compressed pituitary gland
HORMONAL ASSAY
TSH -2.050 (0.27-4.20 mIU/ml)
LH- 7.090 (1.7-8.6mIU/ml)
FSH- 11.05 (1.5-12.4mIU/ml)
Growth hormone -2.8 (0.5-17 ng/l)
Prolactin -6.12 (4.04-15.2ng/ml)
Testosterone- 0.19 (0.26-11.2ng/ml)
KARYOTYPING
------- done at IOG, Egmore
46,XY
FINAL DIAGNOSIS
“ BARDET-BIEDL SYNDROME WITH A
PARTIALLY EMPTY SELLA( PRIMARY) PRESENTING AS HYPOGONADISM”
J Med Genet 1999;36:437-446
doi:10.1136/jmg.36.6.437 Original article “New criteria for improved diagnosis of
Bardet-Biedl syndrome”: results of a population survey
Primary features: Four features are required to be present of: Rod-cone dystrophyPolydactyly Obesity Learning disabilitiesHypogonadism in males Renal anomalies
Three primary plus two secondary features are required of:Secondary features Speech disorder/delay Strabismus/cataracts/astigmatism Brachydactyly/syndactyly Developmental delay Polyuria/polydipsia (nephrogenic diabetes insipidus) Ataxia/poor coordination/imbalance Mild spasticity (especially lower limbs) Diabetes mellitus Dental crowding/ hypodontia/small roots/high arched palate Left ventricular hypertrophy/congenital heart disease Hepatic fibrosis
HYPOGONADISM IN OUR CASE
?
---probably due to primary gonadal failure,secondary to BBS per se
Case reports
The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.
Mozaffarian G, Nakhjavani MK, Farrahi A. Abstract The pathogenesis of hypogonadism and hypogenitalism was investigated
in a male patient with the complete form of the Laurence-Moon-Bardet-Biedl syndrome. Synthetic gonadotropin-releasing hormone induced an increase in serum luteinizing hormone levels from 16.5 mIU/ml to 19.3 mIU/ml and in follicle-stimulating hormone levels from 18.5 mIU/ml to 25.9 mIU/ml. Serum testosterone levels were normal and did not rise after stimulation with human chorionic gonadotropin. The administration of thyrotropin-releasing hormone resulted in an increase in serum thyrotropin levels from 9.0 microU/ml to 12.0 microU/ml. Serum testoterone/estradiol-binding globulin, adrenocorticotropic hormone, and T3 resin uptake were normal. Serum cortisol showed a normal diurnal variation. The sex chromatin test was negative and the karyotupe revealed a 46,XY chromosome pattern. On biopsy, the left testis lacked germinal cells and the right testis showed spermatogenic arrest. Signs of hypogonadism and hypogenitalism persisted after 11 months of testosterone treatment. In this patient the target-organ unresponsiveness resulted in hypogenitalism and hypogonadism.
Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet-Biedl syndrome.
Soliman AT, Rajab A, AlSalmi I, Asfour MG. Source Department of Pediatrics, Royal Hospital, Muscat, Oman. Abstract We evaluated growth parameters and hypothalamic-pituitary-gonadal and growth
functions in five children with Bardet-Biedl syndrome (BBS). Three of the five children had stature below the fifth percentile for age. Their growth hormone (GH) response to provocation was defective, and computed tomographic (CT) scanning revealed empty sellae in all of them. All the children were obese (body mass index [BMI] > 95th percentile for age). Three had hypercholesterolemia. Their basal serum testosterone concentration and testosterone response to 3-day human chorionic gonadotropin (HCG) stimulation were significantly lower than the levels in 12 age-matched obese normal children. Testosterone secretion failed to respond to HCG therapy for 4 weeks. Both basal gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and gonadotropin responses to LH-releasing hormone (LHRH) stimulation were normal and did not differ among the two study groups. It appears that primary hypogonadism is a cardinal feature of BBS, and it may be accompanied by hypothalamic and pituitary abnormalities.
DISCUSSION
Nomenclature: JZ Lawrence RC Moon Bardet
LMBBS Arthur Biedl
Cases reported by Lawrence and Moon --prog. spastic paraparesis and no polydactyly, obesity
Hence the term BARDET BIEDL SYNDROME
prevalence ---- 1 in 1,00,000 Mode of inheritance – 1) Autosomal recessive 2) Multi allelic
inheritance
--- individuals were homozygous /compound heterozygous for mutation at one locus but requires presence of a third heterozygous mutation to manifest phenotype
PATHOGENESIS OF BBS
BBS genes (14) BBS protein(basal body and cilia of
cells)
Assembled to form “BBSome”
Transports intracellular vesicles to base of cilia
plays vital role in ciliary function
CILIOPATHIES
Bardet –Biedl syndrome
primary ciliary dyskinesia
PCKD/Nephronophthisis
Alstrom syndrome
Meckel –gruber syndrome
EVALUATION AFTER DIAGNOSIS
Ophthalmic assessment : visual acuity,field,refractory errors and fundus
BMI Blood pressure pelvic examination and USG Renal function tests and Renal USG Urine analysis –to R/O nephrogenic DI Cardiac evalution-ECG,Chest X-ray,ECHO Developmental assessment
GTT
Lipid profile
Liver function tests
Thyroid function tests
otoacoustic emissions/audiometry
dental examination
neurological assessment
MOLECULAR DIAGNOSIS
14 genes – mapped till now mutations – 1) sequence analysis 2) targeted mutation analysis 3) deletion/duplication analysis
Implications
probands carriers pre-natal diagnosis
TREATMENT MODALITIES
Obesity – dietary mx, exercise, drug therapy for dyslipidemias Cognitive dysfunction,speech disorders – speech
therapy visual disturbances- low vision aids ESRD- renal transplantation In puberty – Hormonal assays and replacement
therapy Poly dactyly – removal of accessory digits cardiac abnormalities, diabetes – guidelines as that of
general population.
FOLLOW UP
6 monthly : urine analysis blood urea ,creatinine blood sugar annual : ophthal evaluation lipid profile,TFT,LFT renal USG`
PRIMARY ESSPRIMARY ESS SECONDARY ESSSECONDARY ESS
there is a hole in membrane covering pituitary gland,sub arachnoid space herniates and compresses pituitary
Incidental finding Hormones : N/mild
hyperprolactinemia no specific treatment
pit. Gland is damaged by tumour ,radiation or
surgeryPseudo tumour cerebri
can cause ESSHormones : deficient Requires replacement
EMPTY SELLA SYNDROME
THANK U