|Year : 2013 | Volume
| Issue : 1 | Page : 29-31
An unusual case of precocious puberty and macroorchidism
Rajeev Philip, Sanjay Saran, Manish Gutch, Kumar K Gupta
Department of Endocrinology, LLRM Medical College, Meerut, Uttar Pradesh, India
|Date of Web Publication||10-Jan-2013|
Department of Endocrinology, G 10, Pg Hostel, LLRM Medical College, Meerut - 250 004, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
The role of thyroid hormone in pubertal development is complex, with majority of the hypothyroid patients failing to attain puberty. However, isosexual precocious puberty with delayed bone age has been described in female hypothyroid patients, and is called Van Wyk Grumbach Syndrome (VWGS). The presentation of VWGS in boys is different, with the major presentation being isolated enlargement of the testes, with no signs of virilisation. The cross over action of Thyroid Stimulating Hormone (TSH) on Follicle Stimulating Hormone (FSH) receptor producing Sertoli cell hyperplasia produces testicular enlargement, and lack of action of TSH on Luteinizing hormone (LH) with no Leydig cell hyperplasia explaining lack of virilisation. Delayed bone age and typical features of hypothyroidism help to differentiate this condition from other causes of precocious puberty.
Keywords: Delayed bone age, incomplete precocious puberty, testiculomegaly, Van Wyk Grumbach Syndrome
|How to cite this article:|
Philip R, Saran S, Gutch M, Gupta KK. An unusual case of precocious puberty and macroorchidism. Thyroid Res Pract 2013;10:29-31
| Introduction|| |
The role of thyroid hormone in pubertal development is complex, with the majority of the hypothyroid patients failing to attain puberty.  However, isosexual precocious puberty with delayed bone age has been described in hypothyroid patients, and is called Van Wyk Grumbach Syndrome (VWGS).  VWGS is described mostly in girls, and seldom in boys. The precocious pubertal development in boys is incomplete, with boys presenting with an isolated enlargement of the testes, with no signs of virilisation.  The pubertal growth spurt is strikingly absent. We report the case of a 16-year-old boy, with history of long standing hypothyroidism, presenting with h/o testicular enlargement with no other sign of virilization.
| Case Report|| |
A 16-year-old boy, presented with h/o enlargement of the testes for the past 8 years. The 2 nd child of a non-consanguineous marriage, had a normal birth and the development in the early childhood was normal. From the age of 8 years, it was noticed that he had an increase in testicular size, with no enlargement of the phallus, no pubic hair development, or development of beard, moustache or axillary hair. He had no history of headache, vomiting, visual disturbances, or galactic seizures. He had history of weight gain, and was less than average at studies.
On examination, his height was 122 cm (less than 3 rd percentile), with weight of 43 Kg, and body mass index of 28.89 Kg/m 2 . His sexual maturity score was Pubic hair (P) stage 1, Axillary hair (A) stage 1 with a testicular volume of 25 ml bilaterally and a stretched penile length of 4.5 cm [Figure 1]. He also had non pitting edema, calf muscle hypertrophy, dry skin, and delayed relaxation of reflexes [Figure 2].
On investigations, he had mild normocytic normochromic anemia with Hb of 8.2 mg/dl, and normal liver function and renal function tests. His bone age was 9.2 years (Tanner Whitehouse two staging). Hormonal analysis revealed autoimmune hypothyroidism, with T4: 1.3 μg/dl (5.01-12.4) T3: 0.29 ng/ml (0.6-1.81), TSH: 880 μiu/ml (0.35-5.50), anti Thyroid Peroxidase Antibody >1300 units/ml (<60.00). His FSH was 6.4 mIU/ml (0.81-8.18) and LH was 0.1 mIU/ml (0.69-7.15). Testosterone 23.86 ng/dl (80-159) and prolactin level 98 ng/ml. (2.80-11.00) Ultrasound testes showed right testis of 23.2 ml and left testes of 24.9 ml with no varicocele. X-ray sella showed enlarged pituitary fossa [Figure 3].
Patient was started on levo thyroxine and 6 months into therapy, his prolactin has normalized, TSH is within target, and is in P3 A2 now. Testicular volume is remaining the same [Figure 4].
|Figure 4: Post treatment- sexual maturity score P3, enlarged testis and normal sized penis|
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| Discussion|| |
Hypothyroidism usually causes delayed puberty, but rarely can cause precocious puberty. The syndrome consisting of primary hypothyroidism and precious puberty has been described since 1905, but the term VWGS was coined in 1960.  Most of the VWGS cases are reported in prepubertal girls with long standing hypothyroidism, who presented with delayed bone age, isosexual precocious puberty and vaginal bleeding.  Most of them had cysts in the ovaries. 
The presentation of VWGS in boys is entirely different, and they present with an isolated enlargement of the testes, without significant signs of virilization. The Phallus enlargement, development of axillary, pubic hair, and morning erections are characteristically absent. The height is short and the bone age delayed, giving a diagnostic clue for differentiating it from other conditions producing sexual precocity. 
The exact cause of development of testicular enlargement is unknown. Van Wyk and Grumbach, who initially described this syndrome, postulated that it is due to lack of specificity in the feedback mechanism leading to an overproduction of multiple hormones.  However, the serum gonadotropin levels are relatively low in this syndrome, to explain the testicular development or precocious puberty in girls. Furthermore, the gonadotropins are immunologically active, but biologically inactive.
It is found that VWGS patients have consistently elevated TSH, and the degree of sexual precocity correlates with the elevation of TSH. Furthermore, patients with secondary or tertiary hypothyroidism do not develop this syndrome. This leads to the postulation that, the high circulating levels of TSH directly acts on FSH receptors mediating sexual precocity. As the TSH only acts on FSH receptors, there is an increase in the number of sertoli cells, leading to testicular enlargement.  As there is no action on LH receptors, there is no Leydig cell hyperplasia, and hence no increased production of testosterone, explaining the lack of development of pubic hair, axillary hair, and penile enlargement.  Myxedematous infiltration of the testes may also contribute to the testicular enlargement. 
The treatment of VWGS is the replacement of thyroid hormone, and the other associated abnormalities like increase in prolactin, enlargement of pituitary will regress with thyroxine replacement. With adequate thyroxine therapy, patient will enter true puberty.
| References|| |
|1.||Styne DM, Grumbach MM. Puberty: Ontogeny, neuroendocrinology, physiology and disorders. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. William's Textbook of Endocrinology. 11 th ed. Philadelphia: Saunders (Elsevier); 2008. p. 969-1166. |
|2.||Van Wyk JJ, Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism. An example of hormonal overlap in pituitary feedback. J Pediatr 1960;57:416-35. |
|3.||Bruder JM, Samuels MH, Bremner WJ, Ridgway EC, Wierman ME. Hypothyroidism-induced macroorchidism: Use of a gonadotropin-releasing hormone agonist to understand its mechanism and augment adult stature. J Clin Endocrinol Metab 1995;80:11-6. |
|4.||Chattopadhyay A, Kumar V, Marulaiah M. Polycystic ovaries, precocious puberty and acquired hypothyroidism: The Van Wyk and Grumbach syndrome. J Pediatr Surg 2003;38:1390-2. |
|5.||Lindsay AN, Voorhess ML, MacGillivray MH. Multicystic ovaries in primary hypothyroidism. Obstet Gynecol 1983;61:433-7. |
|6.||Pringle PJ, Stanhope R, Hindmarsh P, Brook CG. Abnormal pubertal development in primary hypothyroidism. Clin Endocrinol (Oxf) 1988;28:479-86. |
|7.||Anasti JN, Flack MR, Froehlich J, Nelson LM, Nisula BC. A potential novel mechanism for precocious puberty in juvenile hypothyroidism. J Clin Endocrinol Metab 1995;80:276-9. |
|8.||Niedziela M, Korman E. Severe hypothyroidism due to autoimmune atrophic thyroiditis-predicted target height and a plausible mechanism for sexual precocity. J Pediatr Endocrinol Metab 2001;14:901-7. |
|9.||Hansen KA, Tho SP, Hanly M, Moretuzzo RW, McDonough PG. Massive ovarian enlargement in primary hypothyroidism. Fertil Steril 1997;67:169-71. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]