Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine > Khayal - Ant Pituitary/Adrenal Disorders > Flashcards

Khayal - Ant Pituitary/Adrenal Disorders Flashcards

1
Q

Why does the hypothalamus represent the coordinating center of the endocrine system?

A
  • Delivers precise signals to pituitary gland, which releases hormones that affect most endocrine systems in the body
  • Hypothalamus consolidates signals from upper cortical centers, autonomic function, environmental cues and peripheral feedback
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is the vascular supply of the anterior pituitary unique?

A
  • Anterior pituitary lacks major arterial blood supply, making it susceptible to infarction (Sheehan’s Syn)
  • Dense capillary network of pituitary portal blood/plexus containing hypothalamic hormones and the hormones/paracrine/autocrine factors released form the pituitary cells
  • Venous plexus empties into petrosal sinuses, then into the peripheral circulation via the jugular veins
  • In short, this is an exception to the standard vascular supply: venous - capillaries - venous (hypothalamic-hypophyseal portal veinous system)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the embryological origin of the anterior and posterior pituitary?

A
  • Anterior pituitary is derived from the foregut
  • Posterior is derived from neural tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the vascular and neural connections bt the hypothalamus and pituitary.

A
  • PV nucleus: neurons w/terminals in the median eminence, where hormones are released directly into primary capillary plexus, traverse long portal veins in the pituitary stalk, and enter secondary plexus in the anterior pituitary
  • Hypothalamic-hypophyseal portal veinous system: primary plexus, long portal venous system, and secondary plexus
  • SA nucleus: axons travel down supraopticohypophyseal tract and release ADH and oxytocin directly in the posterior pituitary
  • NOTE: this distinction b/t nuclei not important; just understand the uniqueness of the vascular system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the hypothalamic stimulatory and inhibitory hormones? Pituitary correlates?

A
  • CRH: POMC products -> ACTH, MSH, and endorphins (20% of ant pit cells; basophilic)
  • GHRH: GH (50% of ant pit cells; acidophilic)
  • GnRH: LH and FSH (15% ant pit cells; basophilic)
  • TRH: TSH (5% ant pit cells; basophilic)
  • PRH (serotonin, ACTH, opiates, estrogen): prolactin (10-30% ant pit cells; acidophilic)
  • Somatostatin: INH release of growth hormones
  • Dopamine: INH of prolactin release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is hypopituitarism? What are 2 common causes?

A
  • DEC secretion of pituitary hormones that can result from diseases of pituitary or hypothalamus

• Clinical manifestations depend on the cause and the type of hormonal deficiency

  • Pituitary surgery is the most common cause of hypopituitarism
  • Sheehan syndrome: pituitary hypertrophies during pregnancy, blood supply does not -> hypotensive at birth (due to hemorrhage), infarcting the pituitary
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the major causes of hypopituitarism?

A
  • PITUITARY DISEASE: mass lesions (pituitary adenomas, benign tumors, cysts, etc.), pituitary surgery, radiation, infiltrative lesions (lymphocytic hypophysitis, hemochromatosis), infarction (Sheehan syndrome), apoplexy, genetic muts (Pit-1)
  • HYPOTHALAMIC DISEASE: mass lesions (benign - craniopharyngioma, malignant - metastatic from lung, breast), radiation (for CNS, nasopharyngeal malignancies), infiltrative lesions (sarcoidosis, langerhans cell histiocytosis), trauma (fracture of skull base), infectious (TB meningitis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the clinical features of hypopituitarism?

A
  • Varies from asymptomatic to acute collapse, depending on etiology, rapidity of onset, and predominant hormones involved
    1. ACTH def: adrenal insufficiency
    2. TSH def: hypothyroidism
    3. Gonadotropin def: hypogonadism
    4. GH def: failure to thrive, short stature in kids; most adults asymptomatic, but some may have fatigue, weakness, and DEC QOL
    5. Prolactin def: failure of lactation
    6. ADH def: diabetes insipidus (polyuria and polydipsia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the treatment for hypopituitarism?

A

Includes a sum of the tx for each of the individual pituitary hormone deficiencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is growth hormone? When/how is it secreted?

A
  • Main hormone regulating growth -> rapid growth in puberty, for example
  • Secreted in a PULSATILE FASHION
  • Stimulation from the hypothalamus via GHRH, and INH by Somatostatin (also secreted by hypothalamus)
  • Starvation and hypoglycemia are 2 potent stimuli for secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What 2 conditions can GH excess cause?

A
  • Gigantism: growth plates are not fused, resulting in extraordinarily tall stature and other signs of GH excess
  • Acromegaly: growth plates are fused, so other abnormalities of GH will be present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is acromegaly?

A
  • Persistent hypersecretion of GH (most common cause a sematotroph adenoma)
  • Insidious onset & slow progression: avg interval from onset of symptoms to dx 12 years
    1. At dx, 75% have macroadenomas (>10mm), and some extend to para- or suprasellar areas
  • Clinical features due to high serum concentrations of GH and and IGF-1 -> somatic/metabolic effects
    1. Metabolic effects include: nitrogen retention, insulin antagonism, lipolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the causes of acromegaly?

A
  • Primary GH excess: GH-cell adenoma, mixed GH-PRL-cell adenoma, Mammosomatotroph-cell adenoma, Plurihormonal adenoma, GH-cell carcinoma
    1. Familial syndromes: MEN-1, Familial acromegaly, McCune-Albright, Carney’s
  • Ectopic/iatrogenic GH excess: pancreatic islet-cell tumor, lymphoma, iatrogenic
  • GHRH excess: central ectopic (<1%: hypothalamic hamartoma, choristoma, ganglioneuroma), peripheral ectopic (1%: bronchial carcinoid, small cell lung cancer, adrenal adenoma, pheochromocytoma)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the clinical manifestations of acromegaly?

A
  • Direct tumor affects: headache/vision loss (bitemporal hemianopsia: see attached image)
  • Pituitary function: macroadenoma can cause pituitary hormone deficiency by gland compression (most commonly, gonadotropin deficiency)
  • Mortality rate of these pts INC, esp. if strict biochemical control not achieved
    1. INC CARDIOVASCULAR DISEASE mortality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the presenting clinical features of acromegaly?

A
  • More than 50% present with:
    1. Acral enlargement
    2. Maxillofacial changes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the risks of long-term exposure to GH excess?

A
  • Arthropathy: rapid symptomatic improvement, but irreversible bone and cartilage lesions (unrelated to age or GH secretion: usually w/long duration)
  • Neuropathy: peripheral anesthesias, paresthesias, and sensorimotor polyneuropathy, onion bulbs do NOT regress
  • CV: CARDIOMYOPATHY, arrhythmias (LV mass INC, diastolic func DEC), fibrous CT hyperplasia
  • HTN: exacerbates cardiomyopathy, may progress even if GH secretion reduced
  • Pulm: upper airway obstruction via soft tissue overgrowth (improves w/reduced GH secretion)
  • Malignancy: INC risk, INC colon polyps, effect of therapy on risk unknown
  • Carb intolerance: DM, improves w/DEC secretion
  • NOTE: MOST OF THESE IMPROVE WITH TX
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does acromegaly affect your risk of malignancy?

A

INC it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the major diagnostic features of acromegaly?

A
  • SYMPTOMS: headache, heat intolerance, ring and shoe sizes, facial bony changes
  • SIGNS: prominent forehead, broad nose, prominent lower jaw, visual field loss
  • MRI: commonly, macroadenoma
  • BIOCHEM: elevated IGF-1, GH nadir >2 after oral glucose dose
  • PATHO: GH-staining pituitary adenoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do you diagnose pt with acromegaly?

A
  • Measurement of IGF-1 (NOT GH)
  • OGTT: in normal subjects GH levels suppress to <1 ng/ml 2 hours after ingestion of 75 g of glucose
    1. In acromegaly GH levels are >2 ng/ml after an OGTT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the algorithm for acromegaly diagnosis (flow chart)?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do we treat acromegaly?

A
  • Microadenomas, macroadenomas that appear to be fully resectable and macroadenomas causing vision impairment transsphenoidal surgery is the treatment of choice
    1. Macroadenomas abutting or adjacent to the chiasm should be decompressed surgically
    2. Subsequent medical treatment may also be more effective after surgical debulking
  • For others, tx includes a long acting somatostatin analogue or pegvisomant (GH receptor antagonist)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the management strategy for pts with acromegaly (flow chart)?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

A 44-year-old man is evaluated for a 2-year history of headache and 1-year history of diabetes mellitus and hypertension. His glove and shoe sizes have increased several times over the past 3 years, and he reports painful knees and hips. The patient also has sleep apnea and carpal tunnel syndrome. Medications are metformin and lisinopril.

On physical examination, blood pressure is 152/92 mm Hg, pulse rate is 82/min, and respiration rate is 16/min. Coarse facial features, frontal bossing, accentuated nasolabial folds, a large tongue, and thick hands and feet are noted.

What is the most appropriate diagnostic test?

A
  • Serum IGF-1
  • Don’t check GH because it is secreted in a pulsatile fashion (can be high or low depending on when you measure it)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is prolactin?

A
  • Polypeptide hormone produced mainly in ANT pituitary lactotrophs (some o/organs/tissues too)
  • Tonically suppressed by hypothalamic dopamine from tuberoinfundibular cells, tuberohypophyseal dopaminergic system
  • Induces, maintains lactation of the primed breast
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the clinical features of prolactinomas?

A
  • Asymptomatic
  • Hypogonadism (INH LH and FSH)
  • Menstrual abnormalities
  • Infertility
  • Galactorrhea
  • Bone loss secondary to sex steroid hormone attenuation (INH LH and FSH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How do you diagnose prolactinomas?

A
  • Single msmtt of serum prolactin level above upper limit of the normal confirms the diagnosis
    1. Normal prolactin values are generally lower than 25μg/l
    2. Prolactin level >250 μg/l usually indicates the presence of a prolactinoma
    3. Prolactin level >500 μg/l is diagnostic of macroprolactinoma
  • There are some exceptions: some meds can cause very high prolactin levels, like anti-psychotics
  • Tumors can cause stalk compression as well, limiting dopamine release -> hyperprolactinemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do you treat prolactinomas?

A
  • Dopamine agonist therapy:
    1. Lowers prolactin levels
    2. Decreases tumor size
    3. Restores gonadal function
  • ALWAYS, regardless of size
  • For results, see attached
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are prolactinomas?

A
  • Lactotroph adenomas: 40% of all pituitary tumors
  • Normal prolactin levels up to 25; the larger the size of the tumor, the higher the prolactin levels
    1. > 250 μg/l most of the times
    2. Macroprolactinomas (>10 mm in diameter) typically are associated with prolactin levels >250 μg/l (>500 diagnostic of this)
  • Females in their 30s
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the medical therapies for prolactinomas?

A
  • Prolactinoma: Cabergoline, Bromocriptine
  • Adenomas causing acromegaly: Somatostatin analogs (Octreotide, Lanreotide), Cabergoline, Pegvisomant
  • TSH-secreting adenomas: Somatostatin analogs
  • Non-functional adenomas: Cabergoline, Somatostatin analogs
  • NOTE: she skipped the Cushing’s examples from this table
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are TSH-secreting tumors? Dx? Tx?

A
  • TSH- or thyrotropin-secreting pituitary adenomas are the LEAST COMMON type of pituitary tumors
    1. Overproduction of TSH by the pituitary thyrotroph cells
  • Diagnosis is usually made during the evaluation of hyperthyroidism
    1. Biochemical testing reveals an elevated T4 level and an elevated or nonsuppressed TSH level (abnormal + feedback)
    2. Diagnosis is confirmed with a pituitary MRI
  • Often macroadenomas, and the primary therapy is neurosurgical resection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the most common causes of hypopituitarism in adults?

A

Pituitary tumors and their treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

A 58-year-old man is evaluated for a 1-week history of headache that started after he sustained minor head trauma with no loss of consciousness in a motor vehicle collision. A CT scan obtained in the emergency department revealed a sellar mass. The patient has a 2- year history of mild sexual dysfunction but no other symptoms. He takes no medication.

On physical examination, blood pressure is 126/78 mm Hg and pulse rate is 64/min; BMI is 32. Normal secondary sexual characteristics are noted, and no gynecomastia is present. Other examination findings also are normal.

Laboratory studies show normal insulin-like growth factor 1 and morning cortisol levels.

An MRI shows a 1.7-cm sellar mass with suprasellar extension but no chiasmal compression.

In addition to assessing adrenal and thyroid function, what is the most appropriate next diagnostic step?

A

Serum prolactin measurement

33
Q

A 33-year-old woman is evaluated for a 5-month history of amenorrhea and a 3-month history of galactorrhea. The patient says her menstrual cycles were normal before onset of amenorrhea. She takes no medication.

On physical examination, vital signs are normal. Visual field findings are normal. Bilateral galactorrhea is noted.

Results of laboratory studies show a serum luteinizing hormone level of 2 mU/ml (2 units/l), a prolactin level of 965 ng/ml (965 μg/l), and a free thyroxine level of 1.1 ng/dl (14 pmol/l). A serum β-human chorionic gonadotropin measurement is normal.

An MRI shows a 1.5-cm sellar mass with suprasellar extension that impinges on the optic chiasm.

What is the most appropriate initial treatment?

A

Dopamine agonist therapy

34
Q

Most common cause and tx for hyperprolactinemia?

A
  • Most common cause of hyperprolactinemia is a prolactinoma -> 1st line of tx is dopamine agonist
    1. May increase in size during pregnancy, and can lead to visual field defects
  • Note: if female is pregnant, it is normal for her prolactin levels to be elevated
35
Q

24-y/o female brought to hospital by parents bc she told them she is constantly hearing voices that tell her to perform various actions. After brief stay on psych floor, she is prescribed Haloperidol. What is a potential AE?

A

Galactorrhea

  • Pt has sxs suggestive of schizophrenia: associated w/INC Dopamine activity in certain neural pathways
  • Typical antipsychotics like Haloperidol have been shown to block D2 receptors
  • Dopamine antagonism has AEs, like interfering with normal feedback INH of Dopamine in hypothalamic-pituitary axis
  • Since Dopamine INH prolactin secretion, from anterior pituitary, D2 receptor blockade may cause hyperprolactinemia and galactorrhea
36
Q

38-y/o man evaluated for 4-month hx of progressive fatigue, cold intolerance, weight gain, occasional headaches, and loss of libido. He has no polydypsia or polyuria.

PE reveals pale, tired-looking man. BP is low. Pulse 58. RR 12. Deep tendon reflexes have prolonged relaxation phase. All other exam findings non-contributory.

What is going on?

A

Hypothyroidism

  • What should you give simultaneously with Levothyroxine?
    1. GLUCOCORTICOID -> this should be given when thyroid hormone replacement therapy initiated to treat central hypothyroidism to PREVENT PROGRESSIVE ADRENAL INSUFFICIENCY
37
Q

Briefly describe the stimulants, hormones, effects, and feedback mechs of the adrenal cortex and medulla (image).

A
38
Q

Describe the HPA axis pathway/events from the hypothalamic nuclei to the cortisol receptor.

A
  • Inputs to hypothalamic parvocellular nuclei lead to release of CRH into hypophysial portal veins
  • CRH stimulates corticotrophs ant pit to INC release of ACTH into pituitary venous system
  • CRH also stimulates synthesis of new ACTH by activating gene transcription for precursor molecule proopiomelanocortin (POMC) and post-translational processing to ACTH and o byproducts
  • ACTH stimulates release of cortisol by binding melanocyte type-2 receptor (MC2R) in adrenal cortex -> cascade of events and steroidogenesis with cortisol as the main final product
  • Cortisol can circulate in blood in free form (5-6%) or bound primarily to proteins
  • MOA of cortisol, like o/steroid hormones, involves IC receptor and changes in gene transcription and translation
39
Q

What is POMC?

A
  • Proopiomelanocortin: large protein produced by transcription/translation of POMC gene
  • ACTH produced by post-translational processing
  • Other products of POMC can be produced, incl. MSH, which is contained in the sequence for ACTH
  • Ectopic ACTH-producing tumors can perform same processing, but often produce lg amts of precursors, esp. pro-ACTH
40
Q

What factors can INH/stimulate the HPA axis release of ACTH. How does ACTH act molecularly in the adrenal gland?

A
  • Inputs from circadian rhythm generator in supra-chiasmatic nucleus and neural stress pathways in the CNS control the activity of CRH-releasing bodies
  • These neurons are also capable of synthesizing AVP, which can augment pituitary response to CRH
  • ACTH stimulates zona fasciculata and reticularis via MC2R, a GCPR that INC cAMP release, and activates cholesterol transport into mitochondria
41
Q

What is Cushing’s syndrome? What are the two categories of causes, and their sub-causes?

A
  • State of GC excess caused by endogenous production of cortisol by adrenals or exogenous admin of GCS
  • ACTH-dependent Cushing’s:
    1. Excess secretion of ACTH by pituitary corticotroph tumors (Cushing’s disease)
    2. Ectopic ACTH production, usually from neuroendocrine tumors
  • ACTH-independent Cushing’s:
    1. Autonomous adrenal over-production of cortisol, usually due to a benign, solitary adrenal adenoma
    2. Exogenous GCS use
42
Q

What are the signs and symptoms of Cushing’s Syndrome?

A
  • Weight gain, hyperphagia
  • Proximal muscle weakness
  • Easy bruising
  • Violaceous striae
  • Growth retardation children
  • Decreased bone mineral density
  • Psychiatric disturbances
43
Q

List some of the physiological effects of Cushing’s syndrome, and their clinical consequences.

A
  • Hyperphagia/insulin resistance: obesity, glucose intolerance, diabetes, hyperlipidemia (INC lipolysis, hepatic steatosis)
  • Sodium retention (via MR): HTN
  • Cortisol excess: emotional lability, euphoria, depression, psychosis
  • Thinning of skin/CT: striae, bruising
  • Androgen excess: hirsutism, acne
  • INC GFR; suppression of AVP: polyuria (and kidney stones from INC Ca, uric acid, and oxalate in urine + DEC citrate)
  • INH of GnRH, LH, FSH: menstrual disorders, impotence, decreased libido
  • INH of GH secretion: growth retardation
  • INC in bone resorption: osteopenia
  • Catabolic effect on muscle: weakness
44
Q

What do you see here?

A

Striae in Cushing’s syndrome (due to thin skin)

45
Q

What is a good screening test for Cushing’s Syndrome?

A
  • Failure to achieve a normal late night circadian nadir bc this is one of the first measurable derangements that occurs in Cushing’s Syndrome
    1. Any assessment of the HPA axis has to take into account the level of ambient stress -> i.e., be sure pts aren’t suffering from some other kind of stress that is causing their symptoms (this is a relatively uncommon syndrome)
  • REMEMBER: in normal subjects, cortisol peaks in the early AM, and has a nadir (low point) between 11pm and 1am
46
Q

What 4 tests could you do to establish the initial diagnosis of Cushing’s?

A
  • 24-hour urine free cortisol
  • Late-night salivary cortisol
  • 1-mg overnight dexamethasone suppression test: 11pm-12am admin, and msmt the next morning at 8am -> if it does not go below 1.8, there is evidence of hypercortisolism
    1. Note: false (+) rates for in 50% of women taking the oral contraceptive pill because of increased CBG (cortisol binding globulin) levels
  • Longer, low-dose DST (2mg/d for 48 hrs): admin 0.5mg dexamethasone every 6 hrs for 8 doses, and measure serum cortisol 2 or 6 hrs after last dose -> same diagnostic criteria of 1.8 mcg/dL
47
Q

What are the follow-up tests for a Cushing’s diagnosis?

A
  • Measure plasma ACTH level
  • Normal (-) feedback (low ACTH) -> adrenal CT
  • Abnormal (-) feedback (high ACTH) -> pituitary MRI
    1. Clearly abnormal = Cushing disease
    2. Normal/equivocal results -> bilateral petrosal sinus sampling for ACTH with CRH admin
    a. Significant pituitary gradient for ACTH: Cushing disease
    b. No pituitary gradient: occult, ectopic
48
Q

Why is adrenal insufficiency important?

A
  • Adrenal insufficiency arises when cortisol levels are not sufficient to meet the needs of the body
  • Cortisol: aids in maintaining vascular tone, hepatic gluconeogenesis, and maintaining glycogen
    1. Inadequate cortisol in times of stress can lead to hypotension, shock, and hypoglycemia
  • Mineralocorticoid deficiency: renal wasting of Na+, retention of K+, and reduced intravascular volume
49
Q

What is primary adrenal insufficiency?

A
  • Most commonly autoimmune, resulting from chronic destruction of the adrenal cortex
    1. Abs to adrenal cortical antigens are present early in the disease process
  • Typical histologic feature is lymphocytic infiltration
  • Pts with autoimmune adrenal disease more likely to have polyglandular autoimmune systems causing deficiency of o/endocrine glands (like Hashimoto’s)
50
Q

What are the causes of adrenal insufficiency?

A
  • Primary (high ACTH and CRH): autoimmune
    1. Infection: TB, fungal, HIV
    2. Tumors metastatic to adrenals
    3. Infiltration: hemochromatosis
    4. Adrenal hemorrhage
    5. CAH
    6. ACTH resistance syndromes (muts in MC2R)
    7. Surgical: bilateral adrenolectomy for adrenal cancer
  • Secondary (low ACTH, adrenal atrophy): stopping chronic GCS tx (adrenal atrophy)
    1. Hypopituitarism: inadequate ACTH release
    2. After removal of ACTH- or cortisol-secreting tumor (suppression of hypothalamus and normal corticotrophs)
    3. Pituitary apoplexy (cerebral hemorrhage)
    4. Sheehan’s syndrome
    5. Granulomatous disease: Sarcoid
    6. Tumors invading pituitary fossa
    7. Isolated ACTH deficiency (POMC processing defect)
51
Q

What are the clinical features of acute adrenal insufficiency?

A
  • Adrenal crisis should be expected in any pt with acute, unexplained volume depletion and shock
  • May also see hyperkalemia, acidosis, and hypoglycemia
52
Q

What signs, symptoms, and lab findings suggest a cortisol deficiency?

A
  • Primary AND central
  • Fatigue, nausea, weight loss, abdominal pain, arthralgias, low-grade fever
  • Primary disease: hyperpigmentation, slight DEC in BP (unless cortisol deficiency is complete)
    1. Low basal serum cortisol (<5) with suboptimal response to cosyntropin + high plasma ACTH
  • Hyponatremia, azotemia, anemia, leukopenia (high % of eosinophils and lymphos), hypoglycemia
53
Q

What signs, symptoms, and lab findings suggest an aldosterone deficiency?

A
  • Primary only
  • Salt craving, postural dizziness
  • Hypotension, dehydration
  • Low serum aldosterone level and high plasma renin activity
  • Hyponatremia, hypokalemia
54
Q

What signs, symptoms, and lab findings suggest an adrenal androgen deficiency?

A
  • Primary and central
  • Decreased libido
  • DEC pubic/axillary hair (in women only)
  • Low serum DHEA and DHEAS levels
55
Q

What are the clinical features of chronic adrenal insufficiency?

A
  • Typically develops more insidiously
  • Symptoms may include weakness, weight loss, N/V, anorexia, and postural hypotension
  • INC skin pigmentation can be seen with primary adrenal insufficiency secondary to melanocyte stimulating activity associated with ACTH
  • Hyponatremia and hyperkalemia may develop secondary to a lack of aldosterone -> primary adrenal insufficiency more likely to have a lack of aldosterone (than with secondary)
56
Q

How can you diagnose adrenal insufficiency?

A
  • Standard ACTH stimulation test
    1. Draw baseline sample of cortisol
    2. Bolus injection of ACTH 250mcg
    3. Cortisol checked at 30 and 60-min intervals
    4. Cut-off for adequate peak serum cortisol is 18 mcg/dL
57
Q

In acute adrenal insufficiency, you might expect which of the following?

A. Hypertension

B. Hyperkalemia

C. Hypothermia

D. Hyperglycemia

E. Hypernatremia

A

Hyperkalemia

  • Also hypotension, hypoglycemia, and hyponatremia
58
Q

49-y/o F evaluated for 1-wk hx of excessive fatigue and nausea. Hx of HTN, colon cancer, and unexplained anorexia. Tx with MEGESTROL for almost 1 yr, then ran out of meds 2 wks ago.

T 36.5, BP 108/78 with no orthostatic changes, P 86, RR 16, BMI 31. Normal PE. Plethoric round face and central obesity with supraclavicular and posterior cervical fat pads are noted.

Labs normal, except 9am cortisol 2.7, and ACTH also low (8). What is the most appropriate mgmt?

A

Oral hydrocortisone

  • GC deficiency 2 weeks after discontinuing Megestrol, a pro-gestational agent with strong glucocorticoid activity
  • Suppression of HPA axis, so sudden discontinuation can result in symptoms and signs of adrenal insufficiency
59
Q

What is CAH?

A
  • Congenital adrenal hyperplasia: autosomal recessive
  • Defects in steroidogenic pathway, glucocorticoid negative feedback and control of adrenal growth
    1. Defective 17-hydroxyprogesterone to 11-deoxycortisol via 21-hydroxylase = >95% of cases (mutations in the CYP21A2 gene)
  • Usually discovered at birth, and characterized by a hyperplastic adrenal cortex
    1. Can also express itself in adolescence or adulthood -> “non-classic CAH”
60
Q

What are the key parts and products of the normal steroidogenic pathway in the adrenals?

A
  • Main adrenal secretory products:
    1. Aldosterone
    2. Cortisol
    3. Dehydroepiandrosterone (DHEA)
    4. Androstenedione
61
Q

How do F and M with CAH present?

A
  • 21-hydroxylase deficiency results in 1 of 2 clinical syndromes: salt-losing and non-salt-losing (simple virilizing)
  • Girls: ambiguous genitalia + clitoral enlargement
    1. Common urethral-vaginal orifice (urogenital sinus)
    2. Partial or complete fusion of the labia
    3. Internal F reproductive organs normal
    4. May present with a salt-losing adrenal crisis at 1-2 weeks of age
  • Boys: salt-losing adrenal crisis -> hyponatremia, hyperkalemia, and failure to thrive
    1. Or as toddlers with signs of puberty (non-salt-losing form)
    2. Newborn males show no overt signs of CAH, although phallic enlargement and scrotal hyperpigmentation is sometimes present
62
Q

What is the mechanism of virilization in F with CAH?

A
  • DEC production of cortisol, and shift of precursors into the adrenal androgen pathway
  • Bc cortisol (-) feedback is DEC, ACTH release from female pituitary gland INC
  • Although cortisol can eventually be normalized, it is at expense of ACTH-stimulated adrenal hypertrophy and excess fetal adrenal androgen production
63
Q

Appreciate this. Also, know it.

A

Good job!

64
Q

How can you diagnose CAH?

A
  • Characteristic biochemical abnormality for dx in patients with 21-hydroxylase deficiency is elevated serum concentration of 17-hydroxyprogesterone, the normal substrate for 21-hydroxylase
  • A very high serum concentration of 17-hydroxyprogesterone is diagnostic of classic 21-hydroxylase deficiency
  • Most affected neonates have conc >3500 ng/dL
65
Q

What are the signs and symptoms of the 5 different CAH variants?

A
  • Probably only need to know 21-hydroxylase, 11-hydroxylase, and 17-alpha-hydroxylase
66
Q

What is non-classic CAH?

A
  • Defective 17-hydroxyprogesterone to 11-deoxycortisol in patients with CYP21A2 deficiency = DEC cortisol synthesis + INC ACTH secretion
  • Enzymatic activity REDUCED, but sufficient to maintain normal GC and MC production, at the expense of EXCESSIVE androgen production
    1. Less severe form, in which there is 20-50% of 21-hydroxylase enzyme activity, compared with 0-2% in the classic form
  • Salt-wasting is absent and affected females do not have ambiguous genitalia
  • Biochemical findings are less severe than those seen with classic 21-hydroxylase deficiency
67
Q

What are the clinical features of non-classic CAH?

A
  • Does not manifest with neonatal genital ambiguity, but presents later in life w/signs of androgen excess
  • Clinical features in late childhood include:
    1. Premature pubarche (first appearance of pubic hair)
    2. Acne
    3. Accelerated bone age
    4. Adolescent and adult females present with acne, hirsutism, and menstrual irregularity
    5. Although most men w/nonclassic form are thought to have normal testicular function and normal fertility, some do present with testicular adrenal rests and infertility
68
Q

How can you diagnose non-classic CAH?

A
  • ADULT WOMEN: dx strongly suggested by a basal 17- hydroxyprogesterone value >200 ng/dl, and confirmed with an ACTH stimulation test
  • If basal level >200 ng/dl, a high dose (250 mcg) ACTH stimulation test, the GOLD STANDARD for diagnosis, should be performed
  • Response to ACTH is exaggerated in NCCAH, so a serum 17- hydroxyprogesterone value exceeding 1500 ng/dL confirms the diagnosis
69
Q

Describe ion transport in collecting duct principle cells. How does aldosterone affect this?

A
  • ENaC with energy provided by favorable electrochemical gradient for Na+
  • Reabsorbed Na pumped out via Na/K ATPase in basolateral membrane
  • Makes lumen electronegative, favoring K+ secretion into tubule via ROMK in apical membrane
  • Aldo-R enhances Na+ absorption & K+ secretion by INC # of open ENaCs and Na/K pumps
    1. Remember: Spironolactone competes for this receptor
70
Q

Describe the RAAS sequence.

A
71
Q

What is primary hyperaldosteronism?

A
  • Primary hypersecretion of aldosterone is an increasingly recognized cause of hypertension
  • It estimated to be responsible for 5 to 13 percent of hypertension in humans
72
Q

What are the causes of primary hyperaldosteronism?

A
  • Bilateral idiopathic hyperaldosteronism: 60-70%
  • Unilateral aldo-producing adenomas: 30-40%
  • Familial hyperaldosteronism type I (glucocorticoid- remediable aldosteronism [GRA]), type II (the familial occurrence of APA or bilateral IHA or both), and type III (germline mutations in the KCNJ5 potassium channel)
  • Pure aldo-producing adrenocortical carcinomas and ectopic aldosterone-secreting tumors
73
Q

What are the clinical features of primary hyperaldosteronism?

A
  • Hypertension
  • Hypokalemia (inconsistent finding)
  • Metabolic alkalosis
  • Mild hypernatremia
  • Hypomagnesemia
  • Muscle weakness
  • Cardiovascular risks
74
Q

How can you biochemically diagnose primary hyperaldosteronism?

A
  • Simultaneous msmt of morning aldosterone level and plasma renin activity
  • In most pts with hyperaldosteronism, plasma aldo level exceeds 15 ng/dl, but the plasma renin activity is very low or undetectable
  • Ratio of plasma aldo to plasma renin activity >30 has a 90% sensitivity and specificity for diagnosis of primary hyperaldosteronism
    1. Ratio of 20-30 is suggestive of the diagnosis, esp when plasma aldo level is >15 ng/dL
75
Q

What is done after the biochem dx of primary hyperaldosteronism? Why?

A
  • CT of the adrenal gland is performed to define the pathologic cause of primary hyperaldosteronism
  • It can show either a solitary adrenal adenoma or diffuse bilateral adrenal hyperplasia
  • Distinction is important because it affects the method of treatment
76
Q

What is the treatment for primary hyperaldosteronism?

A
  • Primary hyperaldosteronism caused by a solitary aldosterone-secreting adenoma is best treated by adrenalectomy
  • Disease caused by bilateral adrenal hyperplasia is managed medically by using a nonselective (spironolactone) or a more selective (eplerenone) aldosterone blocking agent
77
Q

11-hydroxylase deficiency causes all of the following, except?

A. Hypotension

B. Ambiguous genitalia

C. Cortisol deficiency

D. Metabolic alkalosis

A

Hypotension

78
Q

Woman with hypokalemia on a diuretic for HTN. She is switched to other drugs, but HTN still doesn’t go away. What is the most appopriate next step?

A
  • Serum aldosterone to plasma renin activity ratio is most appropriate next diagnostic test
  • Always start with biochemical tests before imaging in endocrinology

Endocrine (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions