There is no universal agreement regarding reference ranges for TSH and thyroid hormones during pregnancy. For instance, 2011 American Thyroid Association (ATA) guidelines 1 suggested that if trimester-specific reference ranges for TSH are not available, the following reference ranges are recommended: first trimester, 0.1-2.5 mIU/L; second trimester, 0.2-3.0 mIU/L; and third trimester, 0.3-3.0 mIU/L. Such position was repeated in the Endocrine Society 2 and European Thyroid Association guidelines, 3 while subsequent 2017 ATA guidelines 4 suggested a higher cutoff point of TSH 4.0 mIU/L.
Background
SHORT syndrome is an autosomal dominant condition associated severe insulin resistance (IR) and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), where no clear treatment guidelines are available.
Methods
We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test (OGTT) in a 21-year old patient (BMI 17.5 kg/m2), who presented for endocrine assessment with a history of amenorrhoea.
Results
She had lipid concentrations within the reference range, normal thyroid function tests, prolactin, gonadotropins, estradiol and androgens with Free Androgen Index 4.52. Extended Oral Glucose Tolerance Test was performed and showed severe IR. She was then started on metformin 850 mg twice a day, and had repeated OGTT. This showed dramatic worsening of glucose tolerance (e.g. glucose 96 mg/dl versus 187 mg/dl and 68 mg/dl versus 204 mg/dl at 120 and 150 min of OGTT, respectively). This was accompanied by a massive increase of already high insulin concentrations (e.g. from 488.6 to > 1000 µIU/ml, and from 246.8 to > 1000 µIU/ml at 120 and 150 min of OGTT, respectively). Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 µIU/ml versus 100.6 µIU/ml without metformin).
Conclusions
Metformin treatment may paradoxically lead to deterioration of insulin resistance and to development of glucose intolerance in SHORT syndrome. Hence, metformin treatment might be potentially harmful in these patients. Though, the precise cause of such profound and paradoxical worsening of glucose tolerance post metformin remains unknown, SHORT syndrome might prove to be an interesting model to study the mechanism(s) of metformin action.
Background Self-administration of anabolic/androgenic steroids among bodybuilders is an underestimated problem that is either not admitted, or only reluctantly by patients.
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