SGA Hypothalamus & Pituitary

Question 1

Lactotroph adenoma

Answer 1

Prolactin-secreting lactotroph adenomas are the most frequent type of hyperfunctioning pituitary adenoma, accounting for about 30% of all clinically recognized cases. These lesions range from small microadenomas to large, expansile tumors associated with substantial mass effect.

Question 2

Somatotroph adenoma

Answer 2

Growth hormone (GH)-secreting somatotroph adenomas are the second most common type of functioning pituitary adenoma, and cause gigantism in children and acromegaly in
adults. Somatotroph adenomas may be quite large by the time they come to clinical attention because the manifestations of excessive GH may be subtle.

Question 3

Corticotroph adenoma

Answer 3

Excess production of ACTH by
functioning corticotroph adenomas leads to adrenal hypersecretion of cortisol and the development of hypercortisolism (also known as Cushing syndrome).

Question 4

Gonadotroph adenoma

Answer 4

Gonadotroph (LH-producing and FSH- producing) adenomas can be difficult to recognize because they secrete hormones inefficiently and variably, and the secretory products usually do not cause a recognizable clinical syndrome.
They become large enough to cause neurologic symptoms, such as impaired vision, headaches, diplopia, or pituitary apoplexy.

Question 5

Thyrotroph adenoma

Answer 5

Thyrotroph adenoma: Thyrotroph (TSH-producing) adenomas are uncommon, accounting for approximately 1% of all pituitary
adenomas. Thyrotroph adenomas are a rare cause of hyperthyroidism.

Question 6

What are the clinical manifestations of Lactotroph adenomas (Discuss the clinical manifestations with reasoning)?

Answer 6

Increased serum levels of prolactin, or hyperprolactinemia, cause amenorrhea, galactorrhea, loss of libido, and infertility. The diagnosis of an adenoma is made more readily in women than in men (decreased libido and impotence in men), especially between the ages of 20 and 40 years, presumably because of the sensitivity of menses to disruption by hyperprolactinemia. Headache (stretching of the dura by the tumor)
Prolactin inhibits GnRH leading to decreased LH and FSH hormone levels
(leading to decreased estrogen and progesterone hormone levels in women and decreased testosterone levels in men).

Question 7

Somatomedin C (Insulin-like growth factor-1)

Answer 7

Growth hormone producing adenoma (Somatotroph adenoma). Persistently elevated levels of GH stimulate the hepatic(Liver) secretion of insulin-like growth factor 1 (IGF-1) (Somatomedin C).

Question 8

Adrenocorticotrophic hormone (ACTH

Answer 8

Adrenocorticotrophic hormone (ACTH) hormone excess leads to Cushing disease.

Question 9

Prolactin excess leads to

Answer 9

Prolactin excess leads to galactorrhea and hypogonadism

Question 10

Thyroid-stimulating hormone excess leads to

Answer 10

hyperthyroidism

Question 11

Dopamine excess leads to

Answer 11

inhibition of prolactin.

Question 12

What is the most common cause of death in acromegaly?

Answer 12

Most common cause of death - Heart failure due to cardiomegaly and hypertension

Question 13

Laron dwarfism is due to a

Answer 13

Laron dwarfism is due to a congenital absence of growth hormone receptors. Growth hormone binding protein (GHBP), which circulates in the blood, is identical to the extracellular portion of the growth hormone receptor. Plasma levels of GHBP are directly related to tissue expression of the growth hormone receptor. The absence of GHBP in the blood of this child confirms the absence of tissue growth hormone receptor.

Question 14

In Laron dwarfism, plasma concentrations of IGF-1 are

Answer 14

In Laron dwarfism, plasma concentrations of IGF-1 are low because there is no growth hormone receptor on hepatocytes, which secrete most of the blood-borne IGF-1 in response to growth hormone. Plasma growth hormone concentration is increased because of loss of negative feedback effects of growth hormone on the hypothalamus to increase the release of somatostatin into the hypophyseal portal blood. In addition, the negative feedback effects of IGF-1 at the hypothalamus and pituitary are diminished because of the low blood levels of this growth factor.

Question 15

Dwarfing also occurs with

Answer 15

Dwarfing also occurs with growth hormone deficiency due to either hypothalamic or pituitary dysfunction. However, both conditions have decreased GH.

Question 16

What is the treatment for this Laron dwarfism condition?

Answer 16

Treated with IGF-1 analogue MECASERMIN.

Question 17

Radiation induced Hypopituitarism

Answer 17

Due to radiation therapy hypo functioning of the anterior pituitary occurs when approximately 75% of the parenchyma is lost or absent.

Question 18

Hypogonadism and infertility

Answer 18

Hypogonadism and infertility (decreased LH and FSH), hypothyroidism (decreased TSH), hypocortisolism (decreased ACTH) in this patient

Question 19

Prolactinoma

Answer 19

Prolactinoma: Lactotroph adenoma are the most frequent type of hyperfunctioning pituitary adenoma, accounting for about 30% of all clinically recognized cases. These lesions range from small microadenomas to large, expansile tumors associated with substantial mass effect.

Question 20

Sheehan syndrome

Answer 20

Sheehan syndrome: Ischemic necrosis of pituitary secondary to hypotension from postpartum hemorrhage leading to hypopituitarism. Lactotroph cells predominantly affected leading to Prolactin deficiency results in failure of postpartum lactation.

Question 21

Primary adrenal insufficiency presents with

Answer 21

Primary adrenal insufficiency presents with Gradual onset of weakness, skin hyperpigmentation, hypotension (due to salt loss in urine), hypoglycemia, poor response to stress.

Question 22

Craniopharyngioma

Answer 22

Craniopharyngioma: Presents commonly during childhood
with bitemporal hemianopsia or other visual disturbances due to possible compression of optic chiasm; can result in growth retardation, diabetes insipidus.

Question 23

somatostatin analog of 8 amino acids that is 45 times more potent in inhibiting growth hormone secretion but only twice as potent in inhibiting insulin secretion. In addition, it has a much longer half-life of about 80 minutes.

Answer 23

Octreotide

Question 24

Octreotide is used to treat patients with

Answer 24

Octreotide is used to treat patients with acromegaly, which is an uncommon condition caused by excessive growth hormone secretion most often due to a pituitary adenoma.

Question 25

Cosyntropin

Answer 25

Cosyntropin a synthetic form of human corticotropin [ACTH]. Cosyntropin is used in two diagnostic tests. First, it is used to distinguish congenital adrenal hyperplasia from ovarian hyperandrogenism. Second, and more commonly, it is used to diagnose adrenal insufficiency in a test that measures plasma cortisol levels before and after a cosyntropin injection.

Question 26

Desmopressin

Answer 26

Desmopressin, a long-acting synthetic analog of vasopressin. This agent has potent antidiuretic activity but causes less vasoconstriction than natural vasopressin. Desmopressin solutions are available for injection and as a nasal spray that is used to prevent nocturnal urine production and enuresis in patients with diabetes insipidus. Desmopressin overdose can result in dilutional hyponatremia.

Question 27

synthetic GnRH preparations administered continuously to suppress gonadotropin secretion in children with precocious puberty and in adults with prostate cancer, breast cancer, endometriosis, and uterine fibroids.

Answer 27

Goserelin, leuprolide

Question 28

is a recombinant growth hormone preparation used to treat growth hormone deficiency in children with a low growth rate.

Answer 28

Recombinant somatropin is a recombinant growth hormone preparation used to treat growth hormone deficiency in children with a low growth rate.

Question 29

Benign pituitary tumors derived
from Rathke’s pouch remnants (ectoderm). Located suprasellar usually. Caudally into Sella turcica to destroy the gland.
Anteriorly (causing visual field defects).
Superiorly into hypothalamus (increasing intracranial pressure).
Any mass in the suprasellar compartment (e.g., a pituitary
adenoma, craniopharyngioma) may compress the tract extending from the hypothalamus through the pituitary stalk. (modified glial cells and axonal processes) to the posterior lobe of pituitary gland.

Answer 29

Craniopharyngioma

Question 30

is ischemic necrosis of pituitary secondary to hypotension from postpartum hemorrhage leading to hypopituitarism. Lactotroph cells predominantly affected leading to Prolactin deficiency results in failure of postpartum lactation.

Answer 30

Sheehan syndrome

Question 31

Due to radiation therapy hypofunction of the anterior pituitary occurs when approximately 75% of the parenchyma is lost or absent.

Answer 31

Radiation induced Hypopituitarism

Question 32

Decreased urine osmolality

Answer 32

Decreased urine osmolality: Central diabetes insipidus leads
to ADH (antidiuretic hormone) deficiency → hypotonic polyuria leading to decreased urine osmolality (decreased urinary specific
gravity), polydipsia, hypernatremia, and Increased serum osmolality.

Question 33

Increased urine specific gravity is seen in

Answer 33

Increased urine specific gravity is seen in dehydration and SIADH.

Question 34

Increased urine sodium levels is seen in

Answer 34

Increased urine sodium levels is seen in renal failure (renal causes of AKI).

Question 35

How do you differentiate between primary psychogenic
polydipsia, central diabetes insipidus and nephrogenic diabetes insipidus based on tests?

Answer 35

Urine osmolality-300 to 900mOsm/kg H2O) (Serum osmolality-275 to 295mOsm/kg H2O).

Question 36

Water deprivation test should be done first for patients for differentiating all 3 causes of high urinary volume with decreased urine osmolality and increased serum osmolality.

Answer 36

Withhold water for 2 to 3 hours in this patient with urine osmolality (120mOsm/kg)
Measure urinary volume and osmolality (if urinary volume decreases and urine osmolality increases(600mOsm/kg) then primary psychogenic polydipsia).
If urine volume is still high with decreased urine
osmolality (120mOsm/kg), and increased serum osmolality (>295mOsm/kg).
Administer desmopressin injection and check for serum and urine osmolality after 30mins.
Increase urine osmolality from 120 to 400mOsm/kg (>50% increase in osmolality of urine) and decrease in serum osmolality is diagnostic of central diabetes insipidus.
Small (20%) or no increase in urine osmolality and increased serum osmolality is diagnostic of nephrogenic diabetes insipidus.

Question 37

CDI

Answer 37

CDI is caused by lack of ADH production by the hypothalamus. It also presents with polyuria, polydipsia, and low urine osmolarity, but unlike NDI, urine osmolarity would increase (i.e., urine would become more concentrated) after injection of desmopressin.

Question 38

This patient with polyuria (excessive urination) and polydipsia (excessive thirst) on a mood stabilizer has _____________________, likely induced by lithium.

Answer 38

nephrogenic diabetes insipidus

Question 39

most common in cognitively impaired/intellectually disabled patients. It causes polyuria with dilute (low osmolarity) urine; however, water restriction elevates ADH, leading to normal volumes of concentrated urine.

Answer 39

Primary polydipsia (excessive water intake) is most common in cognitively impaired/intellectually disabled patients. It causes polyuria with dilute (low osmolarity) urine; however, water restriction elevates ADH, leading to normal volumes of concentrated urine.

Question 40

involves excessive ADH secretion, which presents with reduced (not increased) urine volume/frequency.

Answer 40

Syndrome of inappropriate ADH secretion (SIADH) involves excessive ADH secretion, which presents with reduced (not increased) urine volume/frequency.

Question 41

What is the treatment of central diabetes insipidus?

Answer 41

Ans:
Desmopressin, which is an ADH analog and is the preferred drug in almost all patients.
Other drugs, such as chlorpropamide, carbamazepine

Question 42

What is the treatment of nephrogenic diabetes insipidus?

Answer 42

Thiazide diuretics — The induction of mild volume depletion with a low- sodium diet plus a thiazide diuretic is a first-line therapy in nephrogenic DI. Amiloride as part of primary therapy to prevent progression of, or possibly improve, lithium-induced DI in patients in whom lithium is continued NSAIDs — Nonsteroidal anti-inflammatory drugs increase urinary concentrating ability by inhibiting the renal synthesis of prostaglandins, which are ADH antagonists. E.g., Indomethacin

Question 43

Hyponatremia due to syndrome of

Answer 43

Hyponatremia due to syndrome of inappropriate
secretion (SIADH) caused by ectopic ADH production by small-cell bronchogenic carcinoma in this patient.

Question 44

Hypernatremia

Answer 44

Central diabetes insipidus leads to ADH (antidiuretic hormone) deficiency → hypotonic polyuria leading to decreased urine osmolality (decreased urinary specific gravity), polydipsia, hypernatremia, and Increased serum osmolality.

Question 45

Hypercalcemia is a cause of

Answer 45

Hypercalcemia is a cause of nephrogenic diabetes insipidus.

Question 46

Hyperkalemia can be seen in

Answer 46

Hyperkalemia can be seen in chronic renal disease.

Question 47

Hypokalemia is a cause of

Answer 47

Hypokalemia is a cause of nephrogenic diabetes insipidus when the levels fall below 3meq/L.

Question 48

How do you treat SIADH?

Answer 48

Moderate symptoms
▪ Fluid restriction (not salt restriction) Moderate - severe symptoms - Pharmacologic
▪ Demeclocycline
▪ Induces ADH insensitivity.
▪ Specifically works at the vasopressin type-2 receptor ▪ Used in patients with small cell carcinoma.
▪ Not routinely used.
▪ Tolvaptan - ADH antagonist [V2R]

Question 49

What are the causes of SIADH?

Answer 49

Causes include pulmonary disorders (COPD, pneumonia), intracranial pathology (trauma, hemorrhage, stroke), pharmacologic agents (antipsychotics, chemotherapy), or pain; may also be caused by ectopic ADH production by small-cell bronchogenic carcinoma and other tumors.

Question 50

What are the laboratory abnormalities seen in SIADH?

Answer 50

Urine osmolality is greater than Plasma Osmolality. • Dilutional hyponatremia
• Increased urinary sodium excretion(>40mEq/L).

Question 51

In precocious puberty, the hypothalamic-pituitary-gonadal axis becomes prematurely active for reasons that are not understood. Treatment involves suppressing gonadotropin secretion with continuous administration of a

Answer 51

long-acting GnRH agonist such as leuprolide.

Question 52

an antagonist of oxytocin receptor used to suppress preterm labor [Not FDA approved]

Answer 52

Atosiban

Question 53

Menotropins, chorionic gonadotropin, follitropin, lutropin, and others are natural or recombinant human gonadotropin preparations used to

Answer 53

induce ovulation in women and spermatogenesis in men.

Question 54

GnRH receptor antagonists used to treat prostate cancer and suppress a premature LH surge during ovulation induction.

Answer 54

Ganirelix, cetrorelix, and degarelix are competitive

Question 55

Dopamine agonists

Answer 55

Dopamine agonists—cabergoline and bromocriptine—are used to suppress prolactin secretion in women with hyperprolactinemia. This condition is often associated with galactorrhea, hypogonadism, and infertility. Cabergoline may also reduce excessive growth hormone secretion in some persons with acromegaly and hyperprolactinemia.