cosyntropin and Hypothyroidism

There is emerging speculation that the inflammatory state associated with SARS-CoV-2 infection may trigger autoimmune conditions, but no causal link is established. There are reports of autoimmune thyroiditis and adrenal insufficiency in adults post-COVID-19. We describe the first pediatric report of adrenal insufficiency and autoimmune hypothyroidism after COVID-19.. A 14-year-old previously healthy girl, with vitiligo, presented in shock following 1 week of fever, lethargy, diarrhea, and vomiting. Three weeks prior, she had congestion and fatigue and known familial exposure for COVID-19. Labs were remarkable for sodium 129 mmol/L, K 4.3 mmol/L, creatinine 2.9 mg/dL, hemoglobin 8.3 g/dL, and positive COVID-19 PCR and SARS-CoV-2 IgG. She was resuscitated with normal saline and required pressor support. EKG showed abnormal repolarization presumed secondary to myocarditis. She met the criteria for multisystem inflammatory syndrome in children (MIS-C), received intravenous immune globulin and IL-1R antagonist and was admitted for intensive care. Persistent hypotension despite improved inflammatory markers and undetectable cortisol led to initiation of hydrocortisone. She was then able to rapidly wean off pressors and hydrocortisone within 48 h. Thereafter, tests undertaken for persistent bradycardia confirmed autoimmune hypothyroidism with TSH 131 μU/mL, free T4 0.85 ng/dL, and positive thyroid autoantibodies. Basal and stimulated cortisol were <1 μg/dL on a standard 250 μg cosyntropin stimulation test, with baseline ACTH >1,250 pg/mL confirming primary adrenal insufficiency. Treatment was initiated with hydrocortisone, levothyroxine, and fludrocortisone. Adrenal sonogram did not reveal any hemorrhage and anti-adrenal antibody titers were positive. The family retrospectively reported oligomenorrhea, increased salt craving in the months prior, and a family history of autoimmune thyroiditis. The cytokine panel was notably different from other cases of MIS-C.. This is the first pediatric report, to our knowledge, of primary adrenal insufficiency and hypothyroidism following COVID-19, leading to a unique presentation of autoimmune polyglandular syndrome type 2. The initial presentation was attributed to MIS-C, but the subsequent clinical course suggests the possibility of adrenal crisis. It remains unknown if COVID-19 had a causal relationship in triggering the autoimmune adrenal insufficiency and hypothyroidism.

Topics: Addison Disease; Adolescent; Adrenal Insufficiency; Adult; Autoantibodies; Child; Cosyntropin; COVID-19; Creatinine; Cytokines; Female; Fludrocortisone; Hashimoto Disease; Humans; Hydrocortisone; Hypothyroidism; Immunoglobulins, Intravenous; Retrospective Studies; Saline Solution; SARS-CoV-2; Sodium; Systemic Inflammatory Response Syndrome; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine

We hypothesized that hypothyroidism and adrenal insufficiency frequently occur together in critically ill patients.. A prospective observational study.. Surgical intensive care unit of a university-affiliated tertiary referral center.. Sixty-six consecutive patients with severe sepsis, septic shock, and hemorrhagic shock who required pulmonary artery catheterization for resuscitation were studied.. Thyrotropin and baseline cortisol levels were obtained at 3 am followed by intravenous injection of 250 mug of cosyntropin, a synthetic adrenocorticotropic hormone derivative. A second measurement of the cortisol level was performed 1 hour later.. Incidence of hypothyroidism and adrenal insufficiency and mortality.. Mean (SD) age was 62 (19) years. The mean (SD) Acute Physiology and Chronic Health Evaluation II score was 21 (5). Twenty-seven patients (40.9%) had severe sepsis, 31 (46.9%) had septic shock, and 8 (12.1%) had hemorrhagic shock. Five patients (7.6%) had hypothyroidism alone and 35 (53.0%) had only adrenal insufficiency. Eight patients (12.1%) had both hypothyroidism and adrenal insufficiency. All patients with endocrine abnormalities were treated. Mortality for the total group was 15 (22.7%) of 66 patients.. There is a 12% incidence of simultaneous hypothyroidism and adrenal insufficiency in our study and the routine testing for both may be indicated in this population of critically ill patients.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Aged; Cosyntropin; Critical Illness; Female; Humans; Hydrocortisone; Hypothyroidism; Incidence; Injections, Intravenous; Male; Middle Aged; Prospective Studies; Sepsis; Shock, Hemorrhagic; Shock, Septic; Thyrotropin; Wounds and Injuries

Idiopathic Addison's disease occurs frequently in association with other organ-specific autoimmune diseases, and autoantibodies to adrenal cortex are markers of this condition. A variable asymptomatic period with subtle adrenal dysfunction may precede the onset of clinical manifestations. We studied the pituitary-adrenal axis by measuring plasma ACTH, cortisol, and 17 alpha-hydroxyprogesterone after ovine CRH (100 micrograms as an iv bolus) stimulation in 19 patients with organ-specific autoimmune disease and adrenal autoantibodies, in whom adrenal steroids were normal under baseline conditions and normally responsive to a standard ACTH stimulation test (250 micrograms). In all subjects, oCRH produced a normal increase in plasma ACTH. Plasma cortisol, which was normoresponsive in 11 subjects, showed little or no increase in 8 subjects. Two of these patients developed overt adrenal failure after 1 yr. The 17 alpha-hydroxyprogesterone response to oCRH, tested in 10 of 19 patients, paralleled that of plasma cortisol, excluding a steroidogenic block at the 21-hydroxylase site. Our data demonstrate the existence of a very early phase of Addison's disease in which adrenal function shows an impaired response to ovine CRH-stimulated ACTH.

Topics: 17-alpha-Hydroxyprogesterone; Addison Disease; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aldosterone; Autoantibodies; Autoimmune Diseases; Corticotropin-Releasing Hormone; Cosyntropin; Diabetes Mellitus, Type 1; Female; Humans; Hydrocortisone; Hydroxyprogesterones; Hypothyroidism; Kinetics; Middle Aged; Thyroiditis, Autoimmune

Hypothyroidism is known to lead to a certain degree of functional insufficiency of the adrenal gland by affecting both the hypophyseal axis and peripheral metabolism of cortisol. This study was conducted to evaluate hypothalamic, pituitary, and adrenal function in a homogeneous group of patients with long-standing major hypothyroidism.. Forty-five patients (32 females, 13 males; mean age 42.9 +/- 9.6 years; range 20-59) with major primary hypothyroidism known to be long-standing (> 1 year in 1 and for an undetermined duration of several years in all the others) were included. Twenty-nine age-matched subjects served as controls. Insulin-induced hypoglycaemia and oral metyrapone tests were performed before and after treatment had induced euthyroidism. Plasma ACTH and cortisol were measured every 20 min for 2 hours during the hypoglycaemia test and ACTH before and after the last dose of metyrapone. Plasma cortisol levels were determined before and 30 min after injection of tetracosactide.. Baseline ACTH and cortisol were not different in patients and controls and were unchanged by treatment. ACTH and cortisol response to hypoglycaemia were weaker in patients with ongoing hypothyroidism (p < 0.05 vs controls) and improved significantly (p < 0.05 vs baseline) after treatment. Adreno-cortical response to exogenous ACTH stimulation was weaker in patients with hypothyroidism (p < 0.05 vs controls) and returned to normal after treatment.. Modifications of the hypothalamic-pituitary-adrenal system resulting from hypothyroidism were minimal and evidenced only by dynamic exploration. Levels returned to normal after adequate treatment and the deficit restricted to the hypothalamus and pituitary might also involve the adrenal gland.

Topics: Adrenocorticotropic Hormone; Adult; Autoimmune Diseases; Cosyntropin; Female; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Hypothyroidism; Insulin; Male; Metyrapone; Middle Aged; Pituitary-Adrenal System; Reference Values

Topics: Adolescent; Adrenal Cortex; Adult; Aged; Cortodoxone; Cosyntropin; Female; Humans; Hydrocortisone; Hydroxylation; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Hormones

The promoting effect of ACTH on carnitine and lipid metabolism was studied in patients with various endocrine hypofunctions. The results were compared with those of normal subjects. In adrenocortical insufficiency, hypothyroidism and hypopituitarism urinary excretion of carnitine was significantly lower than in normal subjects. On intramuscular injection of synthetic beta1-24 ACTH-Z urninary excretion of carnitine in normal subjects increased sixfold on the day of the injection and returned to the pretreatment level on the third day. Serum concentrations of carnitine and FFA increase in parallel with carnitine excretion, while serum triglyceride was lowered in response to ACTH administration. These responses were totally lacking or substantially suppressed in patients with the above endocrine insufficiencies. In hypothyroid and hypopituitary patients substitution therapy restored the responses to ACTH in the same fashion as those in normal subjects. These findings suggest that the promoting effect of ACTH on carnitine and lipid metabolism requires the presence of intact adrenocortical and thyroid functions.

Topics: Addison Disease; Adrenalectomy; Adrenocorticotropic Hormone; Carnitine; Cosyntropin; Fatty Acids, Nonesterified; Humans; Hydrocortisone; Hypopituitarism; Hypothyroidism; Lipids; Prednisolone; Triglycerides; Triiodothyronine