Severe Hypothyroidism Due to Autoimmune Atrophic Thyroiditis - Predicted Target Height and a Plausible Mechanism for Sexual Precocity

Abstract

Autoimmune thyroiditis, the most frequent cause of acquired hypothyroidism in childhood and adolescents, is characterized by raised levels of the specific antibodies to thyroperoxidase (TPOAb) and thyroglobulin (TgAb). We report a girl aged 10 years and 9 months who presented with arrested growth and breast development (thelarche). She also exhibited myxedema of the face and legs, prominent striae on the thighs, dry, cold skin, and hypertrichosis on her back. There was no goiter, no history of thyroid pain and no family history of thyroid disease. She complained occasionally of a transient headache. The patient's height was below the 3rd percentile, while her body weight was at the 50th percentile and bone age was normal. Laboratory tests proved severe hypothyroidism (fT4 0 ng/dl, fT3 0.99 pg/ml, TSH >100 microIU/ml plus an increased titer of TPOAb). Thyroid ultrasound supported the diagnosis of thyroiditis. Pituitary PRL and FSH levels and peripheral estradiol were all elevated. L-Thyroxine therapy, instituted following diagnosis, improved the growth velocity to 11 cm/year and the FSH and E2 levels were normalized to prepubertal values. Complete regression of the breast development was observed within 4 months. However, 4 months later a true (central), isosexual LHRH-dependent puberty started. The pubertal features at the time of the original diagnosis might be explained by: 1. the direct action of elevated TRH on gonadotropes to stimulate gonadotropin secretion and on lactotrophes to stimulate PRL secretion, and 2. TSH action on LH and mostly FSH receptors (homologous to TSH receptors) in the ovary, stimulating the secretion of estradiol.

VanWyk-Grumbach syndrome in a male pediatric patient: A rare case report and literature review

“…Male patients with VWGS have macroorchidism without obvious virilisation, and testicular histology reveals a predominance of tubular structures without increased Leydig cells, in line with an FSH-dominated response (15,26). However, enlargement of gonads and formation of ovarian cysts are usually (3,4,27). Thus, early diagnosis of the disease may help to identify cases that require surgery (5,6).…”

Pericardial Effusion in the Emergency Department

“…Unfortunately, precocious puberty can occur in patients with primary hypothyroidism despite normalization of serum TSH concentrations on L-thyroxine replacement. 16 Overtreatment that results in elevated free thyroxine levels could advance osseous maturation, leading to premature physeal closure which, combined with sexual precocity, predisposes to short adult stature. 17 Careful monitor- L-thyroxine replacement was initiated after obtaining the initial confirmatory sample on day 1; nd, not determined.…”

Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status

“…First, elevated levels of thyrotropin-releasing hormone in hypothyroidism induce hyperprolactinemia and alter GnRH pulsatile secretion, which lead to a delay in luteinizing hormone (LH) response, thus result in delayed puberty 11 . Second, increased thyroid-stimulating hormone (TSH) levels activate gonadal function by stimulating follicle-stimulating hormone (FSH) receptor expressed in gonads, because the structure of FSH and TSH receptors is very similar, which is responsible for precocious puberty 12, 13 . Although some mediators in HPT-HPG interaction have been suggested 11–13 , the mechanism underlying how TH acts on the HPG axis has not been fully elucidated.…”

“…Second, increased thyroid-stimulating hormone (TSH) levels activate gonadal function by stimulating follicle-stimulating hormone (FSH) receptor expressed in gonads, because the structure of FSH and TSH receptors is very similar, which is responsible for precocious puberty 12, 13 . Although some mediators in HPT-HPG interaction have been suggested 11–13 , the mechanism underlying how TH acts on the HPG axis has not been fully elucidated. Additionally, studies on the effect of abnormal thyroid status, hypothyroidism and hyperthyroidism, on reproductive development have produced conflicting results 14, 15 .…”