Weight Gain Infertility and Hypertension

William E. Winter

A 30-year-old African-American woman with a complex medical history presented to her private physician with complaints of emotional lability and depression over the previous 12-18 months. During this period, she gained 25-30 lb (11-14 kg), despite her best attempts to maintain her weight through regular exercise. She also complained of infertility as she had not conceived after a year of unprotected intercourse with her spouse of 10 years. She did have a 5-year-old daughter from her current marriage. That pregnancy was complicated by preeclampsia. At presentation, she reported that her menstrual periods were irregular and in the last 6 months she had had only had two menstrual periods; the last was 6 weeks ago.

Her past medical history was significant for a spontaneous rib fracture 12 months ago. She had reached for a book located on the floor and developed acute chest pain. Chest x-ray in the emergency department revealed the fracture. The fracture was treated conservatively with rest and external support. The radiology report noted some demineralization of the spine and ribs in addition to the fracture. Follow up bone mineral density (BMD) measurements via dexa scan revealed the following findings consistent with a decline in bone mineral density (SD—standard deviation):

Concerning her past medical history, other than tonsillectomy and adenoidectomy at age 6 for recurrent pharyngitis, the patient had no past hospitalizations for medical illnesses. Her childhood illnesses included chicken pox. Other than preeclampsia as noted in her first and only pregnancy, prior to 18 months ago, she reported no serious illnesses. Her immunizations were up-to-date. She took no chronic medications and used no medicinal creams. She denied glucocorticoid use.

Regarding her family history, the patient's 62-year-old mother had migraine headaches. Her 72-year-old father was alive and well. There was no family history of

Location

Lumbar spine Left hip

1.93 SD below the mean 1.18 SD below the mean depression or other forms of psychiatric illness. There was no family history of endocrine disorders including thyroid disease and diabetes mellitus.

Review of systems was positive for polyuria and polydipsia, tiredness, weakness, and easy bruisability. She voided 2-3 times per night. She suffered headaches 1-2 times per week that were relieved with aspirin or acetaminophen. She did not complain of cough, shortness of breath, or wheezing. She did not complain of nausea, vomiting, diarrhea, or constipation. She did report that she always felt hungry.

Physical examination revealed an obese 30-year-old African-American woman who was in no acute distress. Her height was 157 cm, and her weight was 81 kg. Her body mass index was 33kg/m2. Her vital signs were as follows: temperature = 36.5°C, pulse = 95 beats per minute, respirations = 18 breaths per minute, blood pressure = 155/ 95 mm Hg. Repeat blood pressure measurement in the opposite arm revealed 160/92 mm Hg. Her facial appearance was plethoric with prominent checks (i.e., "moon facies"). Mild facial hirsutism involving the temporomandibular areas was identified. Her HEENT examination revealed normal discs and fundi. There was no papilledema or arterial narrowing. There was no thyromegaly or cervical lymphadenopathy. There was a prominent collection of adipose tissue over her upper back below her neck consistent with a "buffalo hump." She had distinct, visible, and palpable supraclavicular fat pads. Her pulmonary and cardiac exams were normal. Her breasts were Tanner stage 4, and no masses or discharge were appreciated. She displayed central adiposity. The abdomen was obese and nontender with normal bowel sounds. By palpation, modest hepatomegaly was appreciated. The spleen was not palpable. The arms and legs were relatively thin and had minimal muscle mass. All peripheral pulses were 2+ and symmetric in the upper and lower extremities. Her pelvic examination was normal. Her skin was oily and slightly wet with perspiration. Neurologic examination revealed decreased strength in the arms and legs. Cranial nerves II-XII were grossly intact. There were no focal neurologic deficits. Her visual fields were intact by confrontation.

Because of her "moon facies," plethora, buffalo hump, supraclavicular fat pads, centripetal obesity, stria, hypertension, and history of depression, infertility, and polyuria/ polydipsia/nocturia, the differential diagnosis of her problems focused on Cushing syndrome.

Baseline CBC and serum and urine chemistries were ordered after an overnight fast. To evaluate the potential cause of infertility, serum prolactin, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured. A 24-hour urinary free cortisol (UFC) concentration was determined to detect hypercortisolism. Like many 24-hour collections, proper sample preservation was necessary.

Reference

Value,

Interval,

Reference

Conventional

Conventional

Value,

Interval,

Analyte

Units

Units

SI Units

SI Units

Sodium

142 mEq/L

135-145

142 mmol/L

135-145

Potassium

3.4 mEq/L

3.5-5.0

3.4 mmol/L

3.5-5.0

Chloride

95 mEq/L

95-105

95 mmol/L

95-105

CO2, total

34 mEq/L

24-32

34 mmol/L

24-32

Creatinine

0.8 mg/dL

0.5-1.2

71 umol/L

44-106

BUN

18 mg/dL

10-20 mg/dL

6.4 mmol urea/L

3.6-7.1

Glucose

128 mg/dL

65-99 mg/dL

7.1 mmol/L

3.6-5.5

Prolactin

18 ng/mL

3-20 ng/mL

18 ug/L

3-20

Testosterone

56 ng/dL

<62 ng/dL

1.94 nmol/L

Estradiol

Urinary free Cortisol

Value, Conventional Units

82 pg/mL

Reference Interval, Conventional Units

<145 pg/mL (follicular phase)

1.1-9.6 mlU/mL (follicular phase)

0.8-25.8 mlU/mL (follicular phase)

216 mg/24 hours 20-90

Value, SI Units

285 pmol/L

Reference Interval, SI Units

<503

(follicular phase)

0.8-25.8 IU/L (follicular phase) 55-248

Her CBC revealed a mild normocytic, normochromic anemia, mild lymphopenia, and no detected eosinophils. Hypokalemia was identified. Her urinalysis was unremarkable except for a urine pH of 5.5 in the freshly voided sample. Based on the elevated total CO2, low normal chloride, and acidified urine, a metabolic alkalosis was apparent. The gonadotropin levels ruled against primary gonadal failure. Neither testosterone or prolactin were elevated.

To supplement the elevated urinary free cortisol measurement, which was consistent with cortisol excess, an overnight dexamethasone suppression test was next performed, with the following results:

Value, Reference Reference

Conventional Interval, Conventional Value, Interval,

Analyte Units Units SI Units SI Units

Cortisol 15 mg/dL <5 414 nmol/L <138

The patient was queried to ensure that she took the prescribed dexamethasone, which she reported that she did.

Together with the patient's history and physical examination (1) the elevated urinary free Cortisol and (2) the elevated postdexamethasone 8:00 am Cortisol were consistent with Cushing syndrome (e.g., hypercortisolism). Recognizing that a variety of conditions can mimic Cushing syndrome ("pseudo-Cushing syndrome"), a "formal" dexamethasone suppression test was performed.

The results of the formal dexamethasone suppression test are given below:

Baseline Baseline Low Dose Low Dose High Dose High Dose Day 1 Day 2 Day 3 Day 4 Day 5 Day 6

Urinary free Cortisol 250 mg 210 mg 175 mg 235 mg 155 mg 145 mg

The degree of UFC suppression on high-dose dexamethasone was borderline. However, basal fasting ACTH concentrations drawn on two consecutive days approximately one week prior to the above formal dexamethasone suppression test revealed measurable ACTH concentrations despite hypercortisolism (note the corresponding elevated am and pm cortisol concentrations with loss of diurnal variation). Measurable ACTH

concentrations would exclude an autonomous source of Cortisol production by the adrenal cortex.

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