Hypopituitarism

Endocrinology, Metabolism and Nutrition

Clinicals - History

Fact Explanation
Features of space occupying lesion Pituitary adenoma causing hypopituitarism act as space occupying lesions giving rise to symptoms such as headache worse in morning, visual disturbances including uni/ bitemporal hemianopia, personality changes, temporal lobe epilepsy Features of space occupying lesion
Pituitary adenoma causing hypopituitarism act as space occupying lesions giving rise to symptoms such as headache worse in morning, visual disturbances including uni/ bitemporal hemianopia, personality changes, temporal lobe epilepsy
Galactorrhea Abnormal secretion of breast milk occurs due to pituitary tumor secreting prolactin or due to pressure on pituitary gland/ stalk resulting in lack of inhibitory hormone of prolactin Galactorrhea
Abnormal secretion of breast milk occurs due to pituitary tumor secreting prolactin or due to pressure on pituitary gland/ stalk resulting in lack of inhibitory hormone of prolactin
Features of acromegaly () Macroadenoma secreting growth hormone (GH) results in excess GH causing symptoms of acromegaly such as prognathism, spade like hands and feet. There would be associated deficiency of other pituitary hormones due to compression of normal tissues thus mixed picture of various hormone excess and deficiency can occur Features of acromegaly ()
Macroadenoma secreting growth hormone (GH) results in excess GH causing symptoms of acromegaly such as prognathism, spade like hands and feet. There would be associated deficiency of other pituitary hormones due to compression of normal tissues thus mixed picture of various hormone excess and deficiency can occur
Features of GH (growth hormone) deficiency. Features such as Reduced muscle mass, strength and energy occur. Typically GH is the first hormone to decrease preceding panhypopituitarism. Features of GH (growth hormone) deficiency.
Features such as Reduced muscle mass, strength and energy occur. Typically GH is the first hormone to decrease preceding panhypopituitarism.
Features of ACTH deficiency Patients with severe fatigue, drowsiness symptoms should be investigated bearing hypopituitarism in mind. Other symptoms such as anorexia, nausea, vomiting, abdominal pain, weight loss, sudden collapse, loss of axillary and pubic hair may also be present. Mild ACTH deficiency may only be unmasked during intercurrent illness. Sudden collapse may occur due to hypoglycaemia or circulatory failure Features of ACTH deficiency
Patients with severe fatigue, drowsiness symptoms should be investigated bearing hypopituitarism in mind. Other symptoms such as anorexia, nausea, vomiting, abdominal pain, weight loss, sudden collapse, loss of axillary and pubic hair may also be present. Mild ACTH deficiency may only be unmasked during intercurrent illness. Sudden collapse may occur due to hypoglycaemia or circulatory failure
Features of gonodotrophins deficiency Such as reduced muscle mass, energy, erectile dysfunction in men; oligo/amenorrhea, dyspareunia, breast atrophy in women; loss of libido, infertility in both Features of gonodotrophins deficiency
Such as reduced muscle mass, energy, erectile dysfunction in men; oligo/amenorrhea, dyspareunia, breast atrophy in women; loss of libido, infertility in both
Features of hypothyroidism Hypothyroidism occur secondary to thyroid stimulating hormone (TSH) deficiency resulting in symptoms of weight gain, cold intolerence, apathy, dry skin and constipation Features of hypothyroidism
Hypothyroidism occur secondary to thyroid stimulating hormone (TSH) deficiency resulting in symptoms of weight gain, cold intolerence, apathy, dry skin and constipation
Symptoms of diabetes insipidus Symptoms such as polyuria, polydipsia, nocturia due to anti diuretic hormone (ADH) deficiency, maybe due to hypothalamic or stalk disorder. Symptoms of diabetes insipidus
Symptoms such as polyuria, polydipsia, nocturia due to anti diuretic hormone (ADH) deficiency, maybe due to hypothalamic or stalk disorder.
Postpartum lactation failure Prolactin deficiency usually due to Sheehan syndrome (usually after postpartum haemorrhage leading to ischemic pituitary necrosis) also maybe due to lymphocytic hypophysitis or pituitary apoplexy Postpartum lactation failure
Prolactin deficiency usually due to Sheehan syndrome (usually after postpartum haemorrhage leading to ischemic pituitary necrosis) also maybe due to lymphocytic hypophysitis or pituitary apoplexy
Pituitary apoplexy Pituitary apoplexy is a medical emergency with symptoms of sudden, severe headache, vomiting, visual loss, cranial-nerve (III, IV, VI) palsy and depressed sensorium occuring due to infarction or haemorrhage into an undiagnosed tumor. High degree of suspicion of cancer (lymphoma ) should be kept in mind while investigating such patients. Pituitary apoplexy
Pituitary apoplexy is a medical emergency with symptoms of sudden, severe headache, vomiting, visual loss, cranial-nerve (III, IV, VI) palsy and depressed sensorium occuring due to infarction or haemorrhage into an undiagnosed tumor. High degree of suspicion of cancer (lymphoma ) should be kept in mind while investigating such patients.
History of head injury Patients usually present within an year of the history of head injury with symptoms of hyptopituitarism History of head injury
Patients usually present within an year of the history of head injury with symptoms of hyptopituitarism
History of postpartum haemorrhage This is associated with ischemic necrosis of the pituitary gland resulting in Sheehan's syndrome History of postpartum haemorrhage
This is associated with ischemic necrosis of the pituitary gland resulting in Sheehan's syndrome
History of radiotherapy Cranial or total body radiation are known to result in hypopituitarism History of radiotherapy
Cranial or total body radiation are known to result in hypopituitarism
Features of haemochromatosis Such as pigmented palmer creases, gums. Hypopituitarism is a known complication of haemochromatosis Features of haemochromatosis
Such as pigmented palmer creases, gums. Hypopituitarism is a known complication of haemochromatosis
Hyposmia /anosmia Associated with Kallman syndrome. Hyposmia /anosmia
Associated with Kallman syndrome.
History of infections Infections such as TB, syphilis and mycoses are known to affect pituitary gland resulting in hypopituitarism History of infections
Infections such as TB, syphilis and mycoses are known to affect pituitary gland resulting in hypopituitarism
Family history of features of hypopituitarism Combined pituitary hormone deficiency has been described by various genetic mutations including some form which is inherited as X linked recessive familial disorder. Family history of features of hypopituitarism
Combined pituitary hormone deficiency has been described by various genetic mutations including some form which is inherited as X linked recessive familial disorder.

Clinicals - Examination

Fact Explanation
Sparse body hair Facial, axillary, chest and pubic hair maybe sparse and pubic hair maybe of female pattern in men due to hypogonadism Sparse body hair
Facial, axillary, chest and pubic hair maybe sparse and pubic hair maybe of female pattern in men due to hypogonadism
Visual field defect Such as bitemporal hemianopia occur due to compression of the optic chiasma by the tumor Visual field defect
Such as bitemporal hemianopia occur due to compression of the optic chiasma by the tumor
Features of hypothyroidism Features of hypothyroidism such as dry skin, loss of lateral eye brow, coarse hair, increased body weight, slow deep tendon reflexes due to thyroid stimulating hormone (TSH) deficiency Features of hypothyroidism
Features of hypothyroidism such as dry skin, loss of lateral eye brow, coarse hair, increased body weight, slow deep tendon reflexes due to thyroid stimulating hormone (TSH) deficiency
Cranial nerve palsies Cranial nerve III, IV and VI lesion causes drooping of eyelids, double vision on lateral vision are associated with large tumors especially the involvement of cranial nerve Cranial nerve palsies
Cranial nerve III, IV and VI lesion causes drooping of eyelids, double vision on lateral vision are associated with large tumors especially the involvement of cranial nerve
Hyperpigmentation Hyperpigmentation is mainly noticed in the skin, palmer creases and gum in haemochromatosis Hyperpigmentation
Hyperpigmentation is mainly noticed in the skin, palmer creases and gum in haemochromatosis
Large hands and feet Due to increased GH, caused by a GH secreting adenoma which compresses the normal gland and cause hypopituitarism otherwise. Large hands and feet
Due to increased GH, caused by a GH secreting adenoma which compresses the normal gland and cause hypopituitarism otherwise.
Galactorrhea Milk maybe expressed from the breast due to underlying prolactinoma Galactorrhea
Milk maybe expressed from the breast due to underlying prolactinoma
Features of gonadotrophin deficiency Such as soft testis, reduced muscle mass, small prostate. Features of gonadotrophin deficiency
Such as soft testis, reduced muscle mass, small prostate.
Features of shock Low blood pressure, tachycardia, cold clammy skin and hypotension are seen in pituitary apoplexy Features of shock
Low blood pressure, tachycardia, cold clammy skin and hypotension are seen in pituitary apoplexy

Investigations - Diagnosis

Fact Explanation
Serum ferritin Elevated in haemochromatosis Serum ferritin
Elevated in haemochromatosis
Human chorionic gonadotrophin (HCG) levels Elevate in germ cell tumors Human chorionic gonadotrophin (HCG) levels
Elevate in germ cell tumors
Serum and CSF angiotensin converting enzyme (ACE) Elevated in sarcoidosis Serum and CSF angiotensin converting enzyme (ACE)
Elevated in sarcoidosis
Insulin tolerance test (ITT) is used to assess peak GH and ACTH levels This is considered as a gold standard test. Contraindicated in patients with ischemic heart disease, arrhythmia, unexplained blackouts and epilepsy. Patient should be carefully monitored during the test. After overnight fast IV insulin of 0.05–0.15 units/kg is given to the patient and blood is drawn at 0, 30, 60, 90, 120 minutes intervals to assess blood glucose, GH and ACTH levels; at hypoglycemia < 2.2 mmol/l, GH level of 5 μg/l and cortisol level of 500 nmol/l is considered normal; peak GH levels less than 3 μg/l (9 mU/l) is considered as severe GH deficiency. Insulin tolerance test (ITT) is used to assess peak GH and ACTH levels
This is considered as a gold standard test. Contraindicated in patients with ischemic heart disease, arrhythmia, unexplained blackouts and epilepsy. Patient should be carefully monitored during the test. After overnight fast IV insulin of 0.05–0.15 units/kg is given to the patient and blood is drawn at 0, 30, 60, 90, 120 minutes intervals to assess blood glucose, GH and ACTH levels; at hypoglycemia < 2.2 mmol/l, GH level of 5 μg/l and cortisol level of 500 nmol/l is considered normal; peak GH levels less than 3 μg/l (9 mU/l) is considered as severe GH deficiency.
Combined growth hormone releasing hormone (GHRH) and arginine test This test is used along with ITT to confirm GH deficiency or used where ITT is contraindicated. Combined growth hormone releasing hormone (GHRH) and arginine test
This test is used along with ITT to confirm GH deficiency or used where ITT is contraindicated.
Combined GHRH and hexarelin tests Hexareline ideally increase GH levels; this test is used in young and middle aged patients with age specific cut offs. Combined GHRH and hexarelin tests
Hexareline ideally increase GH levels; this test is used in young and middle aged patients with age specific cut offs.
Glucagon stimulation test (GST) This can be used to determine both GH and ACTH deficiencies. Glucagon stimulation test (GST)
This can be used to determine both GH and ACTH deficiencies.
IGF1 levels IGF is secreted in response to GH and will be low in GH deficiency, an age specific cut offs should be used for interpretation. Other factors such as hypothyroidism, malnutrition, liver disease and diabetes mellitus also cause low IGF levels, thus interfere with interpretation, if present. IGF1 levels
IGF is secreted in response to GH and will be low in GH deficiency, an age specific cut offs should be used for interpretation. Other factors such as hypothyroidism, malnutrition, liver disease and diabetes mellitus also cause low IGF levels, thus interfere with interpretation, if present.
Free and total thyroxine, TSH levels Low serum thyroxine levels with normal or low TSH points towards TSH deficiency Free and total thyroxine, TSH levels
Low serum thyroxine levels with normal or low TSH points towards TSH deficiency
FSH, LH, oestradiol in women and testosterone in men In men low testosterone with low or normal gonadotrophins and in premenopausal women low oestradiol with no elevation in gonadotrohpins or in postmenopausal women lack of the normal elevation of gonadotrophin indicates gonadotrophin deficiency FSH, LH, oestradiol in women and testosterone in men
In men low testosterone with low or normal gonadotrophins and in premenopausal women low oestradiol with no elevation in gonadotrohpins or in postmenopausal women lack of the normal elevation of gonadotrophin indicates gonadotrophin deficiency
Urine volume and osmolality Increased volume (>40ml/kg/day) and low urine osmolality of <300 mOsmol/kg indicates possible diabetes insipidus due to ADH deficiency. Urine volume and osmolality
Increased volume (>40ml/kg/day) and low urine osmolality of <300 mOsmol/kg indicates possible diabetes insipidus due to ADH deficiency.
Water deprivation test Water is not given to the patient for 8 hours and basal and hourly plasma and urine osmolalities and urine volume is recorded along with body weight which is measured 2 hourly. After 8 hrs IM desmopressin 2 μg is injected and urine and plasma osmolality is remeasured. Urine initially of low osmolality (<300 mOsmol/kg) becomes concentrated (>750 mOsmol/kg) afeter desmopressin injection shows ADH deficiency Water deprivation test
Water is not given to the patient for 8 hours and basal and hourly plasma and urine osmolalities and urine volume is recorded along with body weight which is measured 2 hourly. After 8 hrs IM desmopressin 2 μg is injected and urine and plasma osmolality is remeasured. Urine initially of low osmolality (<300 mOsmol/kg) becomes concentrated (>750 mOsmol/kg) afeter desmopressin injection shows ADH deficiency
Hypertonic saline infusion test This is used where results of water deprivation tests are borderline to confirm ADH deficiency Hypertonic saline infusion test
This is used where results of water deprivation tests are borderline to confirm ADH deficiency
Basal (9 am) cortisol level Level less than 100 nmol/l is considered very low. Basal (9 am) cortisol level
Level less than 100 nmol/l is considered very low.
Short synacthen test Considered the first line test to assess ACTH levels. IM synacthen 250 μg is injected and if 30 minute cortisol level is >550 nmol its considered normal. Short synacthen test
Considered the first line test to assess ACTH levels. IM synacthen 250 μg is injected and if 30 minute cortisol level is >550 nmol its considered normal.
Skull X ray Demonstration of large sella turcica with eroded clinoid process indicate pituitary tumor Skull X ray
Demonstration of large sella turcica with eroded clinoid process indicate pituitary tumor
MRI (magnetic resonance image) of the hypothalamo‐pituitary region with IV gadolinium or a contrast CT head This aids to visualise the tumor MRI (magnetic resonance image) of the hypothalamo‐pituitary region with IV gadolinium or a contrast CT head
This aids to visualise the tumor
Goldmann perimetry Visual field defect such as bitemporal hemianopia may occur due to compression of the optic chiasma by the tumor Goldmann perimetry
Visual field defect such as bitemporal hemianopia may occur due to compression of the optic chiasma by the tumor

Investigations - Management

Fact Explanation
Basic investigations for patients on GH replacement Body weight, Blood pressure, IGF1 levels, fasting glucose, HbA1c, lipid profile, waist‐hip ratio, bone densitometry 2 yrly for those who initially had low bone mineral density are done to monitor the treatment response. Basic investigations for patients on GH replacement
Body weight, Blood pressure, IGF1 levels, fasting glucose, HbA1c, lipid profile, waist‐hip ratio, bone densitometry 2 yrly for those who initially had low bone mineral density are done to monitor the treatment response.
24 hr urine cortisol level. Done in patients who are on glucocorticoid replacement therapy.This is used to detect over replacement of glucocorticoid which could cause harmful side effects 24 hr urine cortisol level.
Done in patients who are on glucocorticoid replacement therapy.This is used to detect over replacement of glucocorticoid which could cause harmful side effects
Serum cortisol levels. This is done for those who are on glucocorticoid replacement therapy to determine subclinical, over or under treatment. An eight hour or modified 3 point curve can be used Serum cortisol levels.
This is done for those who are on glucocorticoid replacement therapy to determine subclinical, over or under treatment. An eight hour or modified 3 point curve can be used
Serum free thyroxine This is used to titrate the thyroxine dose and to assess treatment response along with clinical improvement. Serum free thyroxine
This is used to titrate the thyroxine dose and to assess treatment response along with clinical improvement.
Basic investigations for patients on testosterone replacement Haemoglobin levels, packed cell volume, lipid profile, and prostate specific antigen levels are done Basic investigations for patients on testosterone replacement
Haemoglobin levels, packed cell volume, lipid profile, and prostate specific antigen levels are done
Serum sodium levels Done in patients taking desmopressin whenever the dose is changed. Desmopressin in overdose can cause hyponatremia thus patient should be monitored. Serum sodium levels
Done in patients taking desmopressin whenever the dose is changed. Desmopressin in overdose can cause hyponatremia thus patient should be monitored.
Hormone panel Mandatory to be done after surgery to determine possible post surgical hypopituitarism. Hormone panel
Mandatory to be done after surgery to determine possible post surgical hypopituitarism.
ECG A baseline ECG is obtained prior to an insulin tolerence test, any abnormality in ECG is considered as contraindication for the test ECG
A baseline ECG is obtained prior to an insulin tolerence test, any abnormality in ECG is considered as contraindication for the test
Investigations for pre-operative fitness assessment Chest x-ray, full blood count, renal function tests, blood gases and lung function are the basic investigations done pre operatively. They should be done according to patient's symptoms and according to the particular ASA (American society of anesthesiologists) category the individual patient falls in. Investigations for pre-operative fitness assessment
Chest x-ray, full blood count, renal function tests, blood gases and lung function are the basic investigations done pre operatively. They should be done according to patient's symptoms and according to the particular ASA (American society of anesthesiologists) category the individual patient falls in.

Management - Supportive

Fact Explanation
Patient education This is vital. Patient should be educated regarding the disease and the treatment. Asking patient to double the treatment dose if on glucocorticoid treatment at time of intercurrent illness is essential as it is life saving. Patient education
This is vital. Patient should be educated regarding the disease and the treatment. Asking patient to double the treatment dose if on glucocorticoid treatment at time of intercurrent illness is essential as it is life saving.
Medical alert bracelet This should be worn at all times by patients on glucocorticoid treatment as increased dose would be life saving at times of emergencies Medical alert bracelet
This should be worn at all times by patients on glucocorticoid treatment as increased dose would be life saving at times of emergencies
Pre treatment counselling. Patient should be counselled regarding possible post operative/ radiotherapy hypopituitarism Pre treatment counselling.
Patient should be counselled regarding possible post operative/ radiotherapy hypopituitarism

Management - Specific

Fact Explanation
Treatment of pituitary adenoma. Medical/ surgical therapy and/or radiotherapy is used. The specific modality chosen depends on type of the adenoma, a prolactin secreting macroadenoma responds well to a dopamine agonist whereas a non functioning pituitary adenoma is treated by its surgical removal followed by radiotherapy. Treatment of pituitary adenoma.
Medical/ surgical therapy and/or radiotherapy is used. The specific modality chosen depends on type of the adenoma, a prolactin secreting macroadenoma responds well to a dopamine agonist whereas a non functioning pituitary adenoma is treated by its surgical removal followed by radiotherapy.
Hormone Replacement Therapy Hormone replacement therapy is used to maintain normal hormonal balance of the body. The deficient hormone or the hormone secreted by end organ is given to the patient. Hormone Replacement Therapy
Hormone replacement therapy is used to maintain normal hormonal balance of the body. The deficient hormone or the hormone secreted by end organ is given to the patient.
Treatment of GH deficiency GH is given as 0.27-0.7 mg SC every evening To replace the daily requirement . Adult GH replacement is controversial and policies differ from one country to the other. IGF concentrations are monitored and the dose is titrated accordingly. Treatment of GH deficiency
GH is given as 0.27-0.7 mg SC every evening To replace the daily requirement . Adult GH replacement is controversial and policies differ from one country to the other. IGF concentrations are monitored and the dose is titrated accordingly.
Treatment of ACTH deficiency Hydrocortisone 10 mg on waking up, 5 mg at noon, 5 mg early evening is given. This mimics the ACTH function, the end organ hormone is replaced rather than ACTH itself; glucocorticoid replacement is essential for life while over treatment can cause side effects such as central obesity and low bone mineral density. Treatment of ACTH deficiency
Hydrocortisone 10 mg on waking up, 5 mg at noon, 5 mg early evening is given. This mimics the ACTH function, the end organ hormone is replaced rather than ACTH itself; glucocorticoid replacement is essential for life while over treatment can cause side effects such as central obesity and low bone mineral density.
Treatment of hypothyroidism. Thyroxine 75-150 μg/ day is used to mimic normal function of TSH. A lower dose of 25 μg/ day is used in patients with cardiac disease and in elderly. Patient should be investigated for ACTH deficiency and if present should be treated prior to starting thyroxine. Treatment of hypothyroidism.
Thyroxine 75-150 μg/ day is used to mimic normal function of TSH. A lower dose of 25 μg/ day is used in patients with cardiac disease and in elderly. Patient should be investigated for ACTH deficiency and if present should be treated prior to starting thyroxine.
Treatment for men with gonadotrophin deficiency IM, transdermal, oral, implant, buccal testosterone preparations are available. Any one of these forms can be used. A trial dose is used in women when they have symptoms such as low libido and low sense of wellbeing even after oestrogen replacement when no other explanation can be found to these symptoms. Treatment for men with gonadotrophin deficiency
IM, transdermal, oral, implant, buccal testosterone preparations are available. Any one of these forms can be used. A trial dose is used in women when they have symptoms such as low libido and low sense of wellbeing even after oestrogen replacement when no other explanation can be found to these symptoms.
Treatment for women with gonadotrophin deficiency Oestrogen replacement is achieved by oral or transdermal preparations, some of these may also contains progesterone which is used in patients with intact uterus. Treatment for women with gonadotrophin deficiency
Oestrogen replacement is achieved by oral or transdermal preparations, some of these may also contains progesterone which is used in patients with intact uterus.
Fertility treatment for men and women with gonadotrophin deficiency If pituitary failure is secondary to hypothalamic failure pulsatile GnRH can be given but in men with primary pituitary failure the testosterone replacement is stopped 4 weeks prior and then treated with IM or SC HCG to acheive spermatogenesis, in women treatment with LH activity is necessary to achieve fertility. Fertility treatment for men and women with gonadotrophin deficiency
If pituitary failure is secondary to hypothalamic failure pulsatile GnRH can be given but in men with primary pituitary failure the testosterone replacement is stopped 4 weeks prior and then treated with IM or SC HCG to acheive spermatogenesis, in women treatment with LH activity is necessary to achieve fertility.
Treatment of ADH deficiency. Desmopressin oral or nasal is used Treatment of ADH deficiency.
Desmopressin oral or nasal is used

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