1. NRIMC Endocrinology HYPOPITUITARISM HYPOPITUITARISM Dr Srikanth M.D., D.M. Associate Professor Dept. of Endocrinology NRIAS Dr Sirisha M.D. Senior Resident Dept. of Endocrinology NRIAS

2. NRIMC EndocrinologyHypopituitarism Underdiagnosed entityUnderdiagnosed entity Diagnosis RequiresDiagnosis Requires –High index of suspicion –Low threshold for investigations –Availability of all dynamic endocrine investigations –Endocrine expertise while carrying out investigations Not so rareNot so rare

3. NRIMC Endocrinology. A 26 year old male patient, a product of consangenous parentage presented with consangenous parentage presented with  Growth Retardation  Failure to develop secondary sexual characters normally normally  Decreased frequency of nocturnal erections  Reduced exercise capacity

4. NRIMC Endocrinology  No H/o head injury  No H/o Anosmia / Visual abnormalities  No evidence of Chronic illness / Viral infection  No H/o any drug abuse

5. NRIMC Endocrinology. General Examination:General Examination:  PR – 88/min  BP – 110/70 mm Hg without any postural variation  Weight – 42 Kg  Height – 152 Cm US – 65 cm US – 65 cm LS _ 87 cm LS _ 87 cm Arm span – 158 cms Arm span – 158 cms

6. NRIMC Endocrinology. Genital Examination:Genital Examination:  Pubic Hair – P2  SPL – 10cm  Testes Volume – Prepubertal  No facial hair & hair in other androgen dependent areas  Axillary hair – present but minimal  Other systemic examination is normal  Anosmia –ve, CNS - Normal

7. NRIMC Endocrinology Bone age Bone age -13 yearsBone age -13 years –Delayed –Chronological age – 26 years –Epiphyses – still unfused

8. NRIMC Endocrinology Thyroid function tests ParameterResultUnitsNormal range T30.92ng/ml0.8-1.81 FT32.38pg/ml0.92-11.25 T43.3  gm/dl 4.0 -12.6 FT40.29ng/dl0.89-1.76 TSH11.34  IU/ml 0.35 -5.50 CommentCentral Hypothyroidism / Primary hypothyroidism

9. NRIMC Endocrinology Gonadal axis evaluation ParameterResultUnitsComment FSH0.60mIU/mlLow LH0.29U/LLow Testosterone0.02ng/mlLow ImpressionCentral Hypogonadism

10. NRIMC Endocrinology Growth Axis IGF 1IGF 1 –Active form of GH –< 25 ng/ml –Normal range ( 116-358 ng/ml)

11. NRIMC Endocrinology Adrenal axis evaluation ACTH 27 pg/mlNormalACTH 27 pg/mlNormal Basal cortisol2.0 mcg/dlLowBasal cortisol2.0 mcg/dlLow ParameterResultUnitsComment ACTH27Pg/mlNormal Basal Cortisol2.0  g/dl 4.3- 22.4Low Stim cortisolNot done ImpressionCentral Hypocortisolism !

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13. NRIMC Endocrinology Empty sella appearanceEmpty sella appearance

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15. NRIMC Endocrinology. A 42 year old Female Patient presented withA 42 year old Female Patient presented with Recurrent episodes of facial puffiness of 10 years duration Recurrent episodes of facial puffiness of 10 years duration Dryness of skin associated with scaling & itching Dryness of skin associated with scaling & itching Amenorrhoea of 10 years duration Amenorrhoea of 10 years duration Loss of pubic hair & axillary hair Loss of pubic hair & axillary hair Weakness, fatiguability, depression & impaired memory Weakness, fatiguability, depression & impaired memory Previous H/o PPH and Lactation failure Previous H/o PPH and Lactation failure

16. NRIMC Endocrinology. General ExaminationGeneral Examination Periorbital puffiness Periorbital puffiness Skin – dry, coarse & scaly Skin – dry, coarse & scaly No axillary and pubic hair No axillary and pubic hair Breast atrophy Breast atrophy PR – 90/min PR – 90/min BP – 100/70 mm Hg without postural variation BP – 100/70 mm Hg without postural variation Other Systemic examination is NormalOther Systemic examination is Normal

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18. NRIMC EndocrinologyHemogram Hb 10.6 gm%Hb 10.6 gm% WBC count – 4200WBC count – 4200 Platelets – 2.1 lakhPlatelets – 2.1 lakh DC – normalDC – normal Mild normocytic normocytic anemiaMild normocytic normocytic anemia

19. NRIMC EndocrinologyBiochemistry Creatinine :1.1 mg% (Creatinine :1.1 mg% ( Bilirubin:0.4mg%Bilirubin:0.4mg% SGOT:115U/LSGOT:115U/L SGPT:46U/LSGPT:46U/L SAP:87U/LSAP:87U/L Total protein:7.9gm/dlTotal protein:7.9gm/dl Albumin:4.0gm/dlAlbumin:4.0gm/dl Globulin:3.9gm/dlGlobulin:3.9gm/dl Na:126meq/lNa:126meq/l K:2.6meq/lK:2.6meq/l Parameter Result Normal range

20. NRIMC Endocrinology Thyroid function tests ParameterResultUnitsNormal range T3< 0.01ng/ml0.8-1.81 FT31.03pg/ml0.92-11.25 T4< 0.01  gm/dl 4.0 -12.6 FT40.11ng/dl0.89-1.76 TSH2.38  IU/ml 0.35 -5.50 CommentCentral Hypothyroidism

21. NRIMC Endocrinology Gonadal axis evaluation ParameterResultUnitsComment FSH1.98mIU/mlLow LH< 0.07U/LLow Estradiol28.30pg/mlLow ImpressionCentral Hypogonadism

22. NRIMC Endocrinology Adrenal axis evaluation ParameterResultUnitsComment ACTH10Pg/mlLow Basal Cortisol2.0  g/dl 4.3- 22.4Low Stimulated cortisol- 0 min1.2  g/dl> 20  g/dl Low Stimulated cortisol- 45 min12.8  g/dl> 20  g/dl Low Stimulated cortisol- 60 min10.4  g/dl> 20  g/dl Low Stimulated cortisol- 90 min8.0  g/dl> 20  g/dl Low Stimulation test was done by insulin tolerance test (0.15 U /Kg) ImpressionCentral Hypocortisolism

23. NRIMC Endocrinology Growth Hormone axis evaluation ParameterResultUnitsComment IGF -1 Basal GH< 0.5ng/mlLow Stimulated GH - 0 min< 0.5ng/ml> 10 ng/mlLow Stimulated GH - 45 min< 0.5ng/ml> 10 ng/mlLow Stimulated GH - 60 min< 0.5ng/ml> 10 ng/mlLow Stimulated GH - 90 min< 0.5ng/ml> 10 ng/mlLow Stimulated GH - 120 min< 0.5Ng/ml> 10 ng/mlLow Stimulation test was done by insulin tolerance test (0.15 U /Kg) Peak GH response of > 10 ng/ml is considered normal response ImpressionAdult Growth Hormone deficiency

24. NRIMC Endocrinology Radiological evaluation MRI of pituitary is suggestive of partial empty sella Minimal pituitary tissue is present at floor of sella

25. NRIMC Endocrinology Hypopituitarism HypothyroidismHypogonadismHypocortisolismGH deficiencyLow Prolactin 1.Puffiness 2.Lethargy 3.Coma 4.Weakness 5.Infertility 6.Cramps 7.Can not tolerate LT4 1. Pubertal delay 2. Infertility 3. Amenorrhea * Primary * Secondary 4. Loss of libido 5. Breast atrophy 6. Osteoporosis 1.Weakness 2.Weight loss 3.Lethargy 4.Hypotension 5.Postural hypotension 6.Giddiness 7.Vomitings 8.Diarrhea 9.Pain abdomen 10.Refractory shock 11.Hyponatremia Children 1.Growth failure 2.Shortstature Adults 1.Adult growth hormone deficiency Lactational failure No symptoms in male

26. NRIMC Endocrinology Causes of Hypopituitarism Heriditory Pituitary Hormone deficiency ( Pit 1, Prop 1, LHX 3, HESX1) Acquired Pituitary hormone deficiency –Infections- rare –Infiltrative Primary Hypophysitis ( Lymphocytic, Granulomatous, Xanthomatous) Secondary Hypophysitis ( Histiocytosis X, sarcoidosis ) –Neoplastic Pituitary Tumor and parasellar tumors Craniopharyngioma etc Post Pituitary surgery –Trauma Radiation, surgical resection, brain trauma –Vascular Apoplexy, pregnancy related ( post partum pituitary necrosis), Hypotension

27. NRIMC Endocrinology Summary High index of suspicion is required Low threshold of investigations Seek for endocrine consultation where ever there is a doubt Treatment is difficult –Life threatening hypocortisolemia / hypothyroid coma can occur –Multiple pituitary hormone replacement is needed in physiological manner –Stress advise regarding the steroid replacement is mandatory –Iatrogenic cushings is possible –Constant reinforcement is needed for good complaince –Fertility needs special protocols both in males and females