Hyperprolactinemia, Hypogonadism, SIADH, DI

stimulates milk production, breast development, inhibits ovulation (no GnRH)

What are the functions of prolactin?

dopamine

What inhibits the release of prolactin?

estrogen, TRH, PRH

What stimulates the secretion of prolactin

pregnancy, lactation (dopamine suppression due to oxytocin release), stress

What are some of the physiological processes that cause an increase in serum prolactin?

prolactin inhibits GnRH (No LH/FSH - your body thinks its pregnant)

Why does prolactin lead to hypogonadism?

prolactinomas, decreased prolactin excretion, dopamine suppression (meds, decreased dopaminergic inhibition), chest wall injury

What are some of the pathological processes that cause an increase in serum prolactin?

antipsychotics (1st and 2nd gen), TCA, metoclopramide (reglan), opiates

What are some medications that can lead to hyperprolactinemia?

Serum prolactin

35 y/o male patient presents to the clinic for ED. He also notes a decrease in libido which worries him as he and his partner are trying for a baby. On a physical exam you note gynecomastia with nipple discharge. What do you want to order?

MRI, TSH/T4, BUN/Creatinine, IGF-1, ACTH, prolactin, estradiol, LH, FSH

34 y/o female presents to the clinic with concerns of amenorrhea for the last 6 months. She also reports HA and visual field changes. She states that there is no way she can be pregnant, no new medications or significant medical history. A physical exam shows a lack of peripheral vision. An hcg has come back negative. What else do you want to order?

chiasmal symptoms (mass effect), hypogonadism, bothersome galactorrhea

When is treatment of hyperprolactinemia indicated?

Cabergoline, Bromocriptine (dopamine agonist - decreases prolactin secretion)

1st line treatments for hyperpolactinemia WITHOUT mass effect

Transphenoidal pituitary surgery (followed by radiation if medications are unsuccessful)

1st line treatments for hyperpolactinemia WITH mass effect or dopamine agonist is ineffective, or woman wishing pregnancy

hypogonadism

A decrease in sperm and/or testosterone production relative to age

Primary hypogonandism (hypergonadotropic)

Insufficient testosterone or sperm secretion, but FSH/LH are normal/elevated

secondary hypogonadism (hypogonadotropic)

Insufficient gonadotropin (LH and FSH) secretion resulting in low sperm/testosterone

Leydig (despite elevated LH), Sertoli (despite elevated FSH)

Primary hypogonandism is characterized by a failure of

viral infections, radiation, chemo, autoimmunity, XY gonadal dysgenesis, Klinefelter (XXY)

Causes of Primary hypogonandism

isolated hypogonadotropic hypogonadism (congenital), hypopituitarism, developmental delay

Causes of primary secondary hypogonadism (failure to enter puberty by age 14)

pituitary/hypothalamic tumors, Cushing syndrome, adrenal insufficiency, hypothyroidism, genetic conditions, obesity, poor health

Causes of acquired secondary hypogonadism (normal aging)

appears younger, small genitalia, difficulty gaining muscle mass, lack of beard, failure of voice deepening

What are some signs of hypogonadism in a pre-pubescent male?

Disease of sellar region, medications (steroids, sustained release opioids), HIV associated weight loss, ESRD, COPD, infertility, osteoporosis, type 2 DM

What are the guidelines for screening hypogonadism?

Fasting serum total testosterone

35 y/o male presents to the clinic for a depressed mood. Patient reports that he has no vigor and no libido as well. He notes that he has been going to the gym but is unable to build much muscle and has noticed a decreased in body hair. What lab do you want order initially?

LH, FSH

35 y/o male presents to the clinic for a depressed mood. Patient reports that he has no vigor and no libido as well. He notes that he has been going to the gym but is unable to build much muscle and has noticed a decreased in body hair. Fasting T came back low, what do you want next?

Endocrine workup - (cortisol, MRI, etc)

35 y/o male presents to the clinic for a depressed mood. Patient reports that he has no vigor and no libido as well. He notes that he has been going to the gym but is unable to build much muscle and has noticed a decreased in body hair. Fasting T came back low, LH and FSH are not elevated, what do you want next?

Karyotype testing (primary hypogonadism)

35 y/o male presents to the clinic for a depressed mood. Patient reports that he has no vigor and no libido as well. He notes that he has been going to the gym but is unable to build much muscle and has noticed a decreased in body hair. Fasting T came back low, LH and FSH are elevated, what do you want next?

other pituitary abnormalities, visual field changes, neuro abnormalities

When would you consider getting MRI with hypogonadism

testosterone replacement to normal range, development/maintenance of secondary sexual characteristics

Treatment plan for a hypogonadal male

Topical gels (androgel, testim, fortesta, testrogel, axiron), transdermal patches, striant SR (buccal), testopel (SC), Nastesto (nasal), gonadortropins, weight loss

Medication options for hypogonadism

acne, BPH, sleep apnea, erthrocytosis

ADRs for testosterone replacement

history of prostate/breast cancer, lower UTI, erythrocytosis, heart failure, sleep apnea

C/I for testosterone replacement

SIADH (excess ADH), Diabetes insipidus (ADH deficiency)

Disorders of the posterior lobe

reabsorb water

What is the purpose of vasopressin

vasopressin release, thirst, kidneys responding to vasopressin

Water balance is achieved by

inverse

Describe the relationship between urine osmolality and flow rate

hyponatremia, hypo-osmolatity, urine osmolality above 100 mosmol/kg

What are some red flags for ADH

malignancies, meds, stroke, complication of transsphenoidal pituitary surgery

What are some common causes of SIADH

CMP (Na, osmolality), CBC, UA (osmolality, specific gravity), plasma ADH

75 y/o male patient with a pmhx of stroke 3 months ago presents to the ED for AMS. His daughter reports that he has been confused as well as vomiting. She also states that he has gained weight even though he is not eating as much. Vitals are stable with the exception of bp 155/92. What labs do you want?

Treat underlying cause, Fluid restriction (hypertonic IV if anything), Salt tablets, loop diuretic, vasopressin receptor antagonist (conivaptan, tolvaptan)

75 y/o male patient with a pmhx of stroke 3 months ago presents to the ED for AMS. His daughter reports that he has been confused as well as vomiting. She also states that he has gained weight even though he is not eating as much. Vitals are stable with the exception of bp 155/92. Labs show hyponatremia, low serum osmolality, increased urine osmolality, increased urine specific gravity, and increased plasma ADH. What is your treatment plan?

Diabetes insipidus (DI)

A rare disorder caused by the inability of the kidneys to conserve water, leading to frequent urination and pronounced thirst leading to hypovolemia and dehydration

idiopathic (autoimmune), neurosurgery, trauma, tumors, infiltrative disease

What can cause Central DI (pituitary issue)?

hereditary, renal insufficiency, hypercalcemia, Drugs (lithium, HIV meds, vasopressin antagonist)

What can cause Nephrogenic DI (kidney issue?)

24 hr urine, Vasopressin challenge test, rule out DM, CMP (hypernatremia, hyperosmolality), UA (decreased specific gravity, decreased osmolality), plasma ADH (decreased = central)

Patient presents to the clinic for polyuria and nocturia. They report they have been extremely thirsty since their brain surgery 3 months ago. On a physical exam you not dry skin and mucous membranes and slight hypotension. What Labs do you want?

Measure urine excretion, give desmopressin acetate, measure urine excretion (if urine is more concentrated its central)

Describe the vasopressin challenge test (determines nephrogenic or central)

Desmopressin (nasal or oral)

Treatment plan for central DI

Low solute diet (low sodium, low protein), thiazide diuretic

Treatment plan for nephrogenic DI