Reversible Subclinical Hypothyroidism in the Presence of Adrenal Insufficiency

Hussein D. Abdullatif, MD; Ambika P. Ashraf, MD


Endocr Pract. 2006;12(5):572-575. 

In This Article

Case Reports

Case 1

A 14-year-old boy presented with decline in growth velocity and delayed puberty. He denied having body odor, acne, axillary hair, or pubic hair. Review of systems was negative for salt craving, hyperpigmentation, and fatigability. Physical examination revealed a height at the 50th percentile, weight at the 10th percentile, minimal scrotal hyperpigmentation, no axillary hair, Tanner stage 1 for pubic hair, and testicular volumes of 3 cc (on the right) and 4 cc (on the left). The patient was also at the 50th percentile for height, in accordance with his midparental target height. Findings on evaluation were consistent with primary gonadal failure, with a follicle-stimulating hormone level of 17 mIU/mL (normal adult range, 2 to 9.2), luteinizing hormone level of 53 mIU/mL (normal adult range, 1.5 to 9.0), and serum testosterone concentration of 17 ng/dL, which increased to 23 ng/dL after human chorionic gonadotropin stimulation. His karyotype was negative for Klinefelter's syndrome.

Initially, the patient had a mildly elevated TSH level of 6.61 µIU/mL and normal free FT4 concentration of 1.32 ng/dL. Subsequently, the patient continued to have relatively high TSH levels (maximum, 7.77 µIU/mL), while the FT4 value decreased gradually during a 1-year period to a nadir of 0.83 ng/dL ( Table 1 ). Assessment for antithyroid peroxidase (anti-TPO) antibodies was negative. Lack of adrenarche prompted evaluation of the adrenal hormonal profile, which showed the following: androstenedione 20 ng/dL, testosterone 23 ng/dL, progesterone <10 ng/dL, 17-hydroxyprogesterone <5.0 ng/dL, 17-hydroxypregnenolone 13 ng/dL, 11-deoxycorticosterone <2 ng/dL, dehydroepiandrosterone <10 ng/dL, desoxycortisol <10 ng/dL, and cortisol 1.2µg/dL along with a prolactin level of 21 ng/mL (normal male, 3 to 18). A standard 250-mg cosyntropin stimulation test revealed an elevated baseline adrenocorticotropic hormone (ACTH) level of 1,445 pg/mL (normal, 10 to 60) with a morning plasma cortisol response of less than 1.0 mg/dL, which failed to increase after administration of corticotropin. The plasma renin level was elevated at 934 ng/dL per hour (normal, <330). Assessment for anti-adrenal antibodies and anti-21-hydroxylase antibodies was negative.

The patient was prescribed physiologic replacement doses of hydrocortisone (8 mg/m2 daily) and fludrocortisone. Six weeks later, his FT4 and TSH levels were normal (1.38 ng/dL and 0.5µIU/mL, respectively). He remained euthyroid without receiving thyroid replacement therapy after 4 years of follow-up. Androgen replacement therapy was initiated with testosterone, 25 mg intramuscularly, which was slowly increased to adult replacement doses by monitoring serum testosterone levels.

Case 2

A 12½-year-old girl with type 1 diabetes mellitus had weight and height values at the 10th percentile. At the time diabetes was diagnosed, she had normal FT4 and TSH levels (FT4 1.07 ng/dL and TSH 1.77µIU/mL). Two years later, on routine examination, she was found to have a low FT4 level of 0.79 ng/dL and a high TSH level of 7.66µIU/mL. She had a normal growth velocity of 7.5 cm per year but poor weight gain of 1.7 kg during the previous year. Since the diagnosis of diabetes, the patient had maintained good glycemic control, with a hemoglobin A1c value ranging from 6.5% to 7%. Blood glucose records did not show evidence of hypoglycemia. Adrenal function testing revealed a morning cortisol value of less than 1.0µmg/dL, an elevated ACTH level of 2,495 pg/mL, and an elevated plasma renin level of 701 ng/dL per hour, an indication of both glucocorticoid and mineralocorticoid deficiency. Both anti-TPO antibodies and anti-adrenal antibodies were positive. She denied having any salt craving. Physical examination did not suggest the presence of hyperpigmentation.

The patient became euthyroid (FT4 0.97 ng/dL and TSH 2.69µIU/mL) 1 month later, solely with use of physiologic replacement doses of hydrocortisone (10 mg/m2 daily) and fludrocortisone. She remained euthyroid at latest follow-up (3 years).

Case 3

A 2-year-old girl was found to have hypoglycemiarelated seizures. She had had episodes of tiredness and easy fatigability. Physical examination revealed hyperpigmentation of the skin and oral mucosa; no alacrima or achalasia was present. The patient's weight was in the 97th percentile and height was 4 SD above the 97th percentile. Further evaluation confirmed adrenal insufficiency, with a serum cortisol level of 1µg/dL and an elevated ACTH value of 2,098 pg/mL. The following were normal or negative: electrolytes, plasma renin, aldosterone, very-long-chain fatty acids, and adrenal antibodies. Bilateral adrenal hypoplasia was noted on computed tomographic scan, and no evidence of deletion was detected on DAX1 analysis (fluorescence in situ hybridization at Baylor College of Medicine). Basal and stimulated adrenal profiles were similar: androstenedione <10 ng/dL, testosterone <3.0 ng/dL, progesterone <10 ng/dL, 17-hydroxyprogesterone <5.0 ng/dL, 17-hydroxypregnenolone <10 ng/dL, 11-deoxycorticosterone 12 ng/dL, dehydroepiandrosterone <10 ng/dL, desoxycortisol 16 ng/dL, and cortisol <1µg/dL. On the basis of these laboratory evaluations, familial glucocorticoid deficiency was diagnosed. Results of the initial thyroid function tests suggested mild hypothyroidism (FT4 0.85 ng/dL and TSH 6.25µIU/mL).

Treatment was initiated with hydrocortisone, 10 mg/m2 daily, divided into 3 doses. Two weeks after the initiation of the corticosteroid therapy, the FT4 level increased and TSH decreased to normal (FT4 1.38 ng/dL and TSH 1.7µIU/mL), and they remained normal at 1-year follow-up assessment.


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