A 38-year-old woman was found to have a TSH of 8.9 mIU/L (0.4-4.0) with a low-normal free T4 and positive TPO antibodies, and she started levothyroxine. Ten days later she has vomiting, dizziness and a blood pressure of 84/52 mm Hg, and she has noticed darker skin for several months. Results: sodium 127 mmol/L, potassium 6.0 mmol/L, glucose 58 mg/dL [3.2 mmol/L], 8 AM cortisol 2.4 µg/dL [66 nmol/L], ACTH 780 pg/mL [172 pmol/L] (reference 7-63 pg/mL [1.5-13.9 pmol/L]), plasma renin activity high. Which conclusion best fits these results?

Primary adrenal insufficiency unmasked by thyroxine

Secondary adrenal insufficiency from pituitary failure

Thyrotoxic crisis from an excessive thyroxine dose

Myxedema crisis from undertreated hypothyroidism

A 36-year-old woman has weight gain, wide purple striae and new hypertension. She takes no glucocorticoids. Results: 24-hour urine free cortisol 3.5 times the upper limit on two collections; late-night salivary cortisol raised on two nights; morning ACTH 72 pg/mL [15.8 pmol/L] (reference 7-63 pg/mL [1.5-13.9 pmol/L]); potassium 3.9 mmol/L. Pituitary MRI is normal. Bilateral inferior petrosal sinus sampling gives a central-to-peripheral ACTH ratio of 1.8 at baseline and 5.6 after CRH (diagnostic thresholds 2 or more at baseline, 3 or more after stimulation). What is the most likely source of her cortisol excess?

ACTH-secreting pituitary microadenoma

Pseudo-Cushing state from depression

Cortisol-secreting adrenal adenoma

Ectopic ACTH from a bronchial carcinoid

A 27-year-old woman had a complete hydatidiform mole evacuated 9 weeks ago. Her serum hCG results, all on the same assay, are: week 1, 96,000 mIU/mL [96,000 IU/L]; week 3, 6,400; week 5, 610; week 6, 455; week 7, 470; week 8, 448; week 9, 462 mIU/mL. She uses reliable contraception, and a qualitative urine hCG tested alongside the week 9 serum is positive. Pelvic ultrasound shows no pregnancy. Which interpretation of the hCG results is best?

Post-molar gestational trophoblastic neoplasia

Normal, expected fall after evacuation

Heterophile antibodies in the serum

A new pregnancy after the evacuation

Late-night salivary cortisol is a useful screen for Cushing syndrome because the disorder typically causes:

Loss of the normal late-evening low

A higher early-morning cortisol peak

Faster renal clearance of cortisol

Endocrinology: interpretation - adrenal, pituitary, gonadal and pregnancy

22 ASCP MLS practice questions on Endocrinology: interpretation - adrenal, pituitary, gonadal and pregnancy, part of Chemistry. The first 22 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 38-year-old woman was found to have a TSH of 8.9 mIU/L (0.4-4.0) with a low-normal free T4 and positive TPO antibodies, and she started levothyroxine. Ten days later she has vomiting, dizziness and a blood pressure of 84/52 mm Hg, and she has noticed darker skin for several months. Results: sodium 127 mmol/L, potassium 6.0 mmol/L, glucose 58 mg/dL [3.2 mmol/L], 8 AM cortisol 2.4 µg/dL [66 nmol/L], ACTH 780 pg/mL [172 pmol/L] (reference 7-63 pg/mL [1.5-13.9 pmol/L]), plasma renin activity high. Which conclusion best fits these results?
1. ASecondary adrenal insufficiency from pituitary failure
2. BPrimary adrenal insufficiency unmasked by thyroxine
3. CThyrotoxic crisis from an excessive thyroxine dose
4. DMyxedema crisis from undertreated hypothyroidism
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Answer: B · Primary adrenal insufficiency unmasked by thyroxine
A very low cortisol with a markedly raised ACTH means the adrenal cortex itself has failed, which is primary adrenal insufficiency; the darker skin comes from ACTH and related peptides. High potassium, low sodium and high renin show that aldosterone is also lacking, which does not happen in pituitary disease, where ACTH is low or normal. Thyroid hormone speeds the clearance of cortisol, so starting levothyroxine in untreated adrenal insufficiency can bring on an adrenal crisis. Cortisol deficiency can itself raise TSH mildly, and autoimmune Addison disease often accompanies autoimmune thyroiditis, so glucocorticoid should be replaced before thyroxine when both are present. Neither a myxedema nor a thyrotoxic crisis explains the hyperkalemia or the high ACTH.
- A: Secondary adrenal insufficiency has a low or normal ACTH and spares aldosterone, so potassium stays normal.
- C: Thyrotoxicosis does not cause hyperkalemia, hypoglycemia or a high ACTH.
- D: Her hypothyroidism was mild and is being treated, and myxedema does not raise ACTH or potassium.
Question 2 · Hard
A 36-year-old woman has weight gain, wide purple striae and new hypertension. She takes no glucocorticoids. Results: 24-hour urine free cortisol 3.5 times the upper limit on two collections; late-night salivary cortisol raised on two nights; morning ACTH 72 pg/mL [15.8 pmol/L] (reference 7-63 pg/mL [1.5-13.9 pmol/L]); potassium 3.9 mmol/L. Pituitary MRI is normal. Bilateral inferior petrosal sinus sampling gives a central-to-peripheral ACTH ratio of 1.8 at baseline and 5.6 after CRH (diagnostic thresholds 2 or more at baseline, 3 or more after stimulation). What is the most likely source of her cortisol excess?
1. APseudo-Cushing state from depression
2. BACTH-secreting pituitary microadenoma
3. CCortisol-secreting adrenal adenoma
4. DEctopic ACTH from a bronchial carcinoid
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Answer: B · ACTH-secreting pituitary microadenoma
Repeatedly raised urine free cortisol and late-night salivary cortisol confirm Cushing syndrome, and an unsuppressed ACTH makes it ACTH-dependent. Pituitary MRI misses many small corticotroph adenomas, so petrosal sinus sampling is used to find the source. A central-to-peripheral ratio of 3 or more after CRH, 5.6 here, shows that the ACTH comes from the pituitary; an ectopic tumor gives similar central and peripheral levels. The baseline ratio below 2 does not exclude Cushing disease, because CRH stimulation raises the test's sensitivity. An adrenal adenoma would suppress ACTH, and pseudo-Cushing states seldom give cortisol excess this marked and persistent, which is why sampling is done only after Cushing syndrome is confirmed.
- A: Repeated cortisol excess this marked, with striae, points to true Cushing syndrome.
- C: An adrenal adenoma suppresses ACTH, but her ACTH is raised.
- D: Ectopic ACTH gives a central-to-peripheral ratio below 3 after CRH, not 5.6.
Question 3 · Hard
A 27-year-old woman had a complete hydatidiform mole evacuated 9 weeks ago. Her serum hCG results, all on the same assay, are: week 1, 96,000 mIU/mL [96,000 IU/L]; week 3, 6,400; week 5, 610; week 6, 455; week 7, 470; week 8, 448; week 9, 462 mIU/mL. She uses reliable contraception, and a qualitative urine hCG tested alongside the week 9 serum is positive. Pelvic ultrasound shows no pregnancy. Which interpretation of the hCG results is best?
1. ANormal, expected fall after evacuation
2. BHeterophile antibodies in the serum
3. CA new pregnancy after the evacuation
4. DPost-molar gestational trophoblastic neoplasia
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Answer: D · Post-molar gestational trophoblastic neoplasia
After a molar evacuation, hCG should keep falling steadily until it is undetectable. Here it has stayed between 448 and 470 mIU/mL for four values over 3 weeks, a plateau within about 10%, which meets the FIGO criteria for post-molar gestational trophoblastic neoplasia. A positive urine hCG excludes heterophile antibody interference, because these large antibodies do not pass into urine. A new pregnancy would make hCG rise and would show on ultrasound. The plateau calls for referral for staging and treatment, and hCG remains the marker used to follow the response.
- A: A normal regression keeps falling; four values within 10% over 3 weeks is a plateau.
- B: Heterophile antibodies do not enter urine, yet the urine hCG is positive.
- C: A new pregnancy would make hCG rise and would be seen on ultrasound.
Question 4 · Medium
Late-night salivary cortisol is a useful screen for Cushing syndrome because the disorder typically causes:
1. AA higher early-morning cortisol peak
2. BLoss of the normal late-evening low
3. CLow cortisol-binding globulin
4. DFaster renal clearance of cortisol
Show answerHide answer
Answer: B · Loss of the normal late-evening low
Cortisol normally peaks in the early morning and falls to its lowest point around midnight. In Cushing syndrome this rhythm is lost, so night-time cortisol stays high even when the morning value is near normal. Saliva reflects free cortisol, can be collected at home, and is not affected by binding globulin. Licorice and tobacco can raise the result, and at least two nights are usually tested.
- A: Morning cortisol is often normal or only mildly raised in Cushing syndrome.
- C: Binding globulin is not the cause, and saliva measures free cortisol anyway.
- D: Faster clearance would lower cortisol, not raise it.
Question 5 · Hard
A 24-year-old woman at 10 weeks has vaginal bleeding, severe vomiting and a uterus larger than dates. Results: hCG 450,000 mIU/mL [450,000 IU/L], TSH 0.05 mIU/L, free T4 2.6 ng/dL [33 pmol/L] (reference 0.8-1.8 ng/dL [10-23 pmol/L]). Ultrasound shows no fetus. What is the most likely diagnosis?
1. AMissed early miscarriage
2. BGraves disease in pregnancy
3. CTwin intrauterine pregnancy
4. DComplete hydatidiform mole
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Answer: D · Complete hydatidiform mole
A complete mole is a proliferation of trophoblast with no fetus, so hCG is often far higher than expected for dates and the uterus is large. hCG is structurally similar to TSH, so very high levels stimulate the TSH receptor, suppressing TSH and raising free T4. The same effect, to a lesser degree, causes transient gestational thyrotoxicosis in normal early pregnancy. After evacuation, hCG is followed until undetectable to check for persistent trophoblastic disease.
- A: A missed miscarriage gives a falling, not a very high, hCG.
- B: Graves disease would not explain the huge hCG, the bleeding and the absent fetus.
- C: Twins raise hCG, but the ultrasound would show fetuses.
Question 6 · Hard
A tall 19-year-old man has small firm testes and gynecomastia. Testosterone is 160 ng/dL [5.6 nmol/L] (reference 264-916 ng/dL [9.2-31.8 nmol/L]), and LH and FSH are both well above their reference ranges. Which diagnosis fits best?
1. AKlinefelter syndrome (47,XXY)
2. BAnabolic steroid misuse
3. CKallmann syndrome
4. DProlactin-secreting pituitary adenoma
Answer and explanation in LearnFree account
Question 7 · Medium
Hypertension that is hard to control, potassium 3.0 mmol/L, a raised plasma aldosterone and suppressed renin activity most suggest:
1. ALicorice ingestion
2. BRenal artery stenosis
3. CPrimary aldosteronism
4. DAddison disease
Answer and explanation in LearnFree account
Question 8 · Medium
Serial serum hCG in a woman with pelvic pain about 6 weeks after her last period: 1,200 mIU/mL [1,200 IU/L], then 1,320 mIU/mL [1,320 IU/L] 48 hours later. This change most suggests:
1. AA twin intrauterine pregnancy
2. BAn ectopic or failing pregnancy
3. CA complete hydatidiform mole
4. DA normal intrauterine pregnancy
Answer and explanation in LearnFree account
Question 9 · Medium
Which single blood test is best for screening a patient with suspected acromegaly?
1. AFasting prolactin
2. BRandom growth hormone
3. CInsulin-like growth factor 1
4. DGH after an insulin dose
Answer and explanation in LearnFree account
Question 10 · Hard
A 41-year-old woman who takes no glucocorticoids has weight gain and easy bruising. Results: 24-hour urine free cortisol 4 times the upper limit, late-night salivary cortisol raised, morning plasma ACTH below 5 pg/mL [< 1.1 pmol/L]. The most likely cause is:
1. AEctopic ACTH from a lung tumor
2. BAn ACTH-secreting pituitary tumor
3. CA cortisol-secreting adrenal adenoma
4. DAlcohol-related pseudo-Cushing
Answer and explanation in LearnFree account
Question 11 · Medium
A 9-day-old girl born with ambiguous genitalia is vomiting, with sodium 126 mmol/L and potassium 7.1 mmol/L. The analyte most likely to be markedly raised is:
1. AAldosterone
2. B17-Hydroxyprogesterone
3. C11-Deoxycortisol
4. DCortisol
Answer and explanation in LearnFree account
Question 12 · Hard
A 62-year-old heavy smoker develops weakness, edema and hypertension over 6 weeks. Potassium is 2.6 mmol/L and bicarbonate 35 mmol/L. Cortisol is very high, ACTH is 410 pg/mL [90 pmol/L], and high-dose dexamethasone does not lower cortisol. What is the most likely source?
1. AAldosterone-producing adenoma
2. BPituitary corticotroph adenoma
3. CSmall cell lung carcinoma
4. DAdrenocortical carcinoma
Answer and explanation in LearnFree account
Question 13 · Easy
A woman taking which drug is most likely to have a raised serum prolactin?
1. ARisperidone
2. BHydrocortisone
3. CLevothyroxine
4. DCabergoline
Answer and explanation in LearnFree account
Question 14 · Easy
In the United States today, the most common cause of primary adrenal insufficiency (Addison disease) is:
1. AAutoimmune adrenalitis
2. BPituitary adenoma
3. CAdrenal tuberculosis
4. DSteroid withdrawal
Answer and explanation in LearnFree account
Question 15 · Hard
Maternal serum AFP is 2.6 MoM, calculated for 16 weeks from the last menstrual period; the screen-positive cutoff is 2.5 MoM. Ultrasound then shows a single normal fetus at 18 weeks. What should be done next?
1. AReport a raised risk of a neural tube defect
2. BRecalculate the MoM using the ultrasound dates
3. CAsk for a repeat sample in 4 weeks
4. DMeasure amniotic fluid acetylcholinesterase now
Answer and explanation in LearnFree account
Question 16 · Easy
Pregnancy immunoassays avoid cross-reaction with LH, FSH and TSH by using antibodies against hCG's:
1. AAlpha subunit
2. BReceptor-binding region
3. CBeta subunit
4. DCarbohydrate side chains
Answer and explanation in LearnFree account
Question 17 · Hard
A 35-year-old woman at 16 weeks, dated by ultrasound and carrying a single fetus, has these quad screen results: AFP 0.65 MoM, unconjugated estriol 0.70 MoM, hCG 2.4 MoM, inhibin A 2.2 MoM. Which condition do these results put at increased risk?
1. ATrisomy 21
2. BTrisomy 18
3. CSmith-Lemli-Opitz syndrome
4. DOpen neural tube defect
Answer and explanation in LearnFree account
Question 18 · Hard
A 45-year-old woman has fatigue, headaches and no periods for 8 months. She takes no medicines. Results: sodium 132 mmol/L, potassium 4.3 mmol/L, 8 AM cortisol 2.5 µg/dL [69 nmol/L], ACTH 6 pg/mL [1.3 pmol/L] (reference 7-63 pg/mL [1.5-13.9 pmol/L]). Cosyntropin raises cortisol only to 10 µg/dL [276 nmol/L] (normal peak 18 µg/dL [497 nmol/L] or more). The best interpretation is:
1. ALow cortisol-binding globulin
2. BPrimary adrenal insufficiency
3. CSecondary adrenal insufficiency
4. DNonclassic adrenal hyperplasia
Answer and explanation in LearnFree account
Question 19 · Medium
Which result set fits untreated primary adrenal insufficiency (Addison disease)?
1. ACortisol high, ACTH high, potassium low
2. BCortisol low, ACTH high, potassium high
3. CCortisol low, ACTH low, potassium normal
4. DCortisol high, ACTH low, potassium low
Answer and explanation in LearnFree account
Question 20 · Medium
On a second-trimester quad screen, which pattern is typical of trisomy 18?
1. AAFP and uE3 low; hCG and inhibin A high
2. BAFP high; other markers normal
3. CAFP, uE3 and hCG all low
4. DuE3 very low; AFP and hCG normal
Answer and explanation in LearnFree account
Question 21 · Hard
A 30-year-old woman with regular periods and no galactorrhea has a prolactin of 68 ng/mL [68 µg/L] (reference < 25 ng/mL [< 25 µg/L]). Pituitary MRI is normal. After polyethylene glycol (PEG) precipitation, prolactin recovery is 22%. The best explanation is:
1. AMostly macroprolactin
2. BPrimary hypothyroidism
3. CA pituitary microadenoma
4. DUnrecognized early pregnancy
Answer and explanation in LearnFree account
Question 22 · Hard
Which test is appropriate for screening a patient for Cushing syndrome?
1. APlasma renin activity and aldosterone
2. BOvernight 1 mg dexamethasone suppression test
3. CA single random morning serum cortisol
4. DAn ACTH (cosyntropin) stimulation test
Answer and explanation in LearnFree account

Endocrinology: interpretation - adrenal, pituitary, gonadal and pregnancy

Late-night salivary cortisol is a useful screen for Cushing syndrome because the disorder typically causes:

A 24-year-old woman at 10 weeks has vaginal bleeding, severe vomiting and a uterus larger than dates. Results: hCG 450,000 mIU/mL [450,000 IU/L], TSH 0.05 mIU/L, free T4 2.6 ng/dL [33 pmol/L] (reference 0.8-1.8 ng/dL [10-23 pmol/L]). Ultrasound shows no fetus. What is the most likely diagnosis?

A tall 19-year-old man has small firm testes and gynecomastia. Testosterone is 160 ng/dL [5.6 nmol/L] (reference 264-916 ng/dL [9.2-31.8 nmol/L]), and LH and FSH are both well above their reference ranges. Which diagnosis fits best?

Hypertension that is hard to control, potassium 3.0 mmol/L, a raised plasma aldosterone and suppressed renin activity most suggest:

Serial serum hCG in a woman with pelvic pain about 6 weeks after her last period: 1,200 mIU/mL [1,200 IU/L], then 1,320 mIU/mL [1,320 IU/L] 48 hours later. This change most suggests:

Which single blood test is best for screening a patient with suspected acromegaly?

A 41-year-old woman who takes no glucocorticoids has weight gain and easy bruising. Results: 24-hour urine free cortisol 4 times the upper limit, late-night salivary cortisol raised, morning plasma ACTH below 5 pg/mL [< 1.1 pmol/L]. The most likely cause is:

A 9-day-old girl born with ambiguous genitalia is vomiting, with sodium 126 mmol/L and potassium 7.1 mmol/L. The analyte most likely to be markedly raised is:

A 62-year-old heavy smoker develops weakness, edema and hypertension over 6 weeks. Potassium is 2.6 mmol/L and bicarbonate 35 mmol/L. Cortisol is very high, ACTH is 410 pg/mL [90 pmol/L], and high-dose dexamethasone does not lower cortisol. What is the most likely source?

A woman taking which drug is most likely to have a raised serum prolactin?

In the United States today, the most common cause of primary adrenal insufficiency (Addison disease) is:

Maternal serum AFP is 2.6 MoM, calculated for 16 weeks from the last menstrual period; the screen-positive cutoff is 2.5 MoM. Ultrasound then shows a single normal fetus at 18 weeks. What should be done next?

Pregnancy immunoassays avoid cross-reaction with LH, FSH and TSH by using antibodies against hCG's:

A 35-year-old woman at 16 weeks, dated by ultrasound and carrying a single fetus, has these quad screen results: AFP 0.65 MoM, unconjugated estriol 0.70 MoM, hCG 2.4 MoM, inhibin A 2.2 MoM. Which condition do these results put at increased risk?

Which result set fits untreated primary adrenal insufficiency (Addison disease)?

On a second-trimester quad screen, which pattern is typical of trisomy 18?

A 30-year-old woman with regular periods and no galactorrhea has a prolactin of 68 ng/mL [68 µg/L] (reference < 25 ng/mL [< 25 µg/L]). Pituitary MRI is normal. After polyethylene glycol (PEG) precipitation, prolactin recovery is 22%. The best explanation is:

Which test is appropriate for screening a patient for Cushing syndrome?