Long-standing Primary Hypothyroidism Research Articles

How Should I Take My Levothyroxine?

How Should I Take My Levothyroxine?

Van wyk-grumbach syndrome: an unusual presentation of long-standing primary hypothyroidism mimicking ovarian tumor

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SUN-433 Pituitary Dysfunction Secondary to a Large Cavernous Internal Carotid Artery Aneurysm

Background: Intracranial aneurysms extending into the sellar space and leading to pituitary dysfunction are exceedingly rare. This type of vascular lesions may be responsible for less than 0.2% of cases of hypopituitarism. Herein, we present a case of hypopituitarism and hyperprolactinemia secondary to a large unruptured left cavernous internal carotid artery aneurysm with intra- and suprasellar extension. Clinical case: An 81-year-old woman with past medical history of long-standing primary hypothyroidism was noted to have a suppressed serum TSH (0.007 uU/mL [0.400 - 5.500]) on routine laboratory studies. Prior to this, she had been on a stable dose of levothyroxine replacement for several years and her TSH level had been maintained within the normal reference range. Subsequent laboratory studies showed an elevated prolactin level (173.4 ng/mL [4.5 - 26.8]), inappropriately low gonadotropin levels for a post-menopausal woman (FSH 4.4 mU/mL [20 - 100]; LH 0.8 mU/mL [>20]), normal IGF-1 (96 ng/mL [27 - 170]), and a low morning cortisol level (2.5 ug/dL (5.3 - 22.5)] with an inappropriately normal ACTH level (12 pg/mL [<47]). Her 60-minute cortisol level was <20 ug/dL during an ACTH stimulation test. The patient was started on steroid replacement and was continued on levothyroxine. A brain MRI was performed and demonstrated an area of heterogeneous unenhanced T1-weighted signal intensity and T2 signal void in the sellar space, measuring approximately 15 mm in diameter. The radiological differentials included a proteinaceous pituitary cyst or a vascular aneurysm. A brain MRA was then obtained for better characterization of the lesion, which revealed a large left cavernous internal carotid artery aneurysm (13 x 17 x 16 mm), completely filling the sellar space and extending into the suprasellar region. The patient was referred to neurosurgery and underwent a successful pipeline embolization of the aneurysm. At two months follow-up, her TSH was 0.159 uU/mL and her prolactin level was 140.3 ng/mL. Conclusion: Aneurysms with intrasellar extension should always be considered in the differential diagnosis of sellar lesions. When compared with cases of nonfunctioning pituitary macroadenomas, intrasellar aneurysms may result in comparable dysfunction in pituitary hormone production and hyperprolactinemia. Endocrine abnormalities are usually irreversible and permanent hormone replacement therapy is necessary. Long-term follow-up may elucidate pituitary function recovery after effective aneurysm treatment.

Does One Size Fit Everyone? Replacement Dose of Levothyroxine in Long-standing Primary Hypothyroidism in Adults.

Objectives:The recommended starting dose of levothyroxine (LT4) in primary hypothyroidism is 1.6 μg/kg body weight and is based on presumption of minimal residual thyroid function in autoimmune hypothyroidism. This study aimed at finding the range and determining factors for LT4 dose in long-standing hypothyroidism.Methods:A cross-sectional study of individuals with primary autoimmune hypothyroidism on LT4 replacement was done between March 2015 and January 2016. Individuals enrolled were euthyroid based on recent serum thyroid-stimulating hormone. The inclusion criteria included LT4 intake in the morning empty stomach, maintenance of at least 1-h food gap, not on medications known to hamper LT4 absorption within 4 h of dosing, diagnosis of hypothyroidism at least for 1 year, and on a minimum 25 μg LT4. P < 0.05 was considered statistically significant.Results:A total of 346 individuals (290 women and 56 men; 214 premenopausal and 76 postmenopausal women) were enrolled. The mean duration of hypothyroidism and age were 5.7 years and 42.1 years, respectively. The range and mean of absolute LT4 daily dose (ADD), LT4 dose based on body weight (D/W), and LT4 dose based on ideal body weight (D/IBW) were 25–200 μg daily and 77.1 μg, 0.3–2.82 μg/kg and 1.21 μg/kg, and 0.42–3.5 μg/kg and 1.58 μg/kg, respectively. Duration of hypothyroidism was significant predictors of ADD, D/W, and D/IBW. Gender-based difference in ADD and D/IBW was explained by gender difference in anthropometry.Conclusion:Long-standing primary autoimmune hypothyroidism has variable dose requirement of LT4 for achieving euthyroidism and may be dependent on the degree of residual functional thyroid. Duration of hypothyroidism was significant positive predictor for either ADD, D/W, or D/IBW.

Primary hypothyroidism presenting as a pituitary macroadenoma and precocious puberty

The association in young females of long-standing primary hypothyroidism, isosexual precocious pseudopuberty, and multicystic enlarged ovaries was first described in 1960 by Van Wyk and Grumbach. In this case study, we report a girl with precocious puberty, poor linear growth, decreased vision, and a large pituitary pseudotumor due to long-standing hypothyroidism with regression of all components following thyroxine (T4) supplementation. This girl aged 12 years and 3 months presented in Endocrinology Department with complaints of early menarche starting at the age of 8 years with normal cycles along with early progressive breast development starting almost simultaneously. On examination, she had a reduced growth for age ( 150 μIU/ml (0.35–5.5) and a free T4 (FT4) and free triiodothyronine below normal limits suggestive of primary hypothyroidism. Furthermore, serum prolactin levels were elevated along with an elevated serum follicle-stimulating hormone, luteinizing hormone, and estradiol. Multicystic ovaries and a bulky uterus on ultrasound were suggestive of precocious puberty. Magnetic resonance imaging scan of the sella turcica was suggestive of a pituitary macroadenoma. Posttreatment with gluten-free diet, iron supplements, and T4 replacement, her thyroid function, hemoglobin, and prolactin normalized along with a regression in the size of the ovary. Therefore, in patients of this age presenting with a pituitary macroadenoma, anemia, precocious puberty, and primary hypothyroidism, medical management was preferred over neurosurgical intervention so as to avoid permanent hypopituitarism and lifelong hormone replacement therapy.

Van Wyk Grumbach Syndrome-A rare case report

Van Wyk and Grumbach syndrome is a rare condition characterized by breast development, uterine bleeding and multicystic ovaries in the presence of long-standing primary hypothyroidism. The patient with this syndrome was admitted in Shaheed Suhrawardy Medical College Hospital in November 2013. Here this rare and interesting case was reported.Journal of Current and Advance Medical Research 2015;2(1):24-27DOI: http://dx.doi.org/10.3329/jcamr.v2i1.22586

Male Child with Van Wyk-Grumbach's Syndrome and Other Complications of Long-Standing Primary Hypothyroidism: A Case Report

Primary hypothyroidism in the juvenile population generally leads to retardation of linear growth and delay or even arrest of puberty. However, in rare conditions, children with long-standing hypothyroidism present with signs of Van Wyk-Grumbach's syndrome (VWGS) which include juvenile hypothyroidism, delayed bone age, and pseudoprecocious puberty. We report a rare case of prepubertal male child from Asian origin, presented with long-standing untreated hypothyroidism complicated with VWGS and other complications including obesity, short stature, hepatomegaly, asymptomatic mild pericardial effusion, and pituitary hyperplasia.

An unusual presentation of acquired hypothyroidism: the Van Wyk–Grumbach syndrome

The association in young females of long-standing primary hypothyroidism, isosexual precocious pseudopuberty and multicystic enlarged ovaries was first described in 1960 by Van Wyk and Grumbach. Since then, sporadic case reports have contributed to clarifying the key features of this syndrome. The unique elements that lead to this diagnosis are FSH-dominated sexual precocity combined with a delayed bone age in the presence of hypothyroidism. It is important to recognise this syndrome because initiating simple thyroid hormone replacement completely resolves symptoms and hormone abnormalities, avoiding unnecessary investigations for malignancies or surgical intervention. We describe an 8-year-old girl with autoimmune thyroiditis and severe long-standing hypothyroidism presenting with the clinical features of Van Wyk-Grumbach syndrome, a secondary TSH-secreting adenoma and hyperprolactinaemia. In addition, this girl presented with microcytic anaemia, elevated erythrocyte sedimentation rate (ESR) and two unusual features - a newly developed streaky hyperpigmented skin lesion and parathyroid hormone suppression despite vitamin D deficiency. Thyroxine replacement normalised all hormone abnormalities and shrunk the pituitary adenoma within 9 months, but the new skin lesion persisted. We review the literature and explore the pathophysiology of known and new features that give rise to speculation indicating stimulation of the FSH G protein-coupled receptor by excessive TSH, but LH suppression by hyperprolactinaemia.

A case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto's thyroiditis

Myxedema coma (MC) is a rare, but often fatal endocrine emergency. The majority of cases that occur in elderly women with long-standing primary hypothyroidism are caused by particular triggers. Conversely, MC of central origin is extremely rare. Here, we report a case of MC with both central and primary origins. A 56-year-old woman was transferred to our hospital due to loss of consciousness; a chest x-ray demonstrated severe cardiomegaly. Low body temperature, bradycardia, and pericardial effusion suggested the presence of hypothyroidism. Endocrinological examination revealed undetectable levels of serum free thyroxine (T(4)) and free triiodothyronine (T(3)), whereas serum thyroid-stimulating hormone (TSH) levels were not elevated. The woman's serum anti-thyroid peroxidase antibody and anti-thyroglobulin antibody tests were positive, indicating that she had Hashimoto's thyroiditis. Provocative tests to the anterior pituitary revealed that she had TSH and growth hormone (GH) deficiency; however, GH levels were restored after supplementation with levothyroxine for 5 months. This was not only a rare case of MC with TSH deficiency and Hashimoto's thyroiditis; the patient also developed severe osteoporosis and possessed transient elevated levels of serum carcinoembryonic antigen (CEA). This atypical case may suggest the role of anterior pituitary hormone deficiencies, as well as hypothyroidism, in the regulation of bone metabolism.

Index of Suspicion

Index of Suspicion

Macroorquidismo: a propósito de un caso

Macroorchidism is a rare condition in children and is usually associated with fragile X syndrome. Other possible etiologies of macroorchidism are long-standing primary hypothyroidism, adrenal remnants in congenital adrenal hyperplasia, follicle stimulating hormone (FSH)-secreting pituitary macroadenomas, local tumors, lymphomas, and aromatase deficiency. Bilateral macroorchidism can be a normal variant in adult men. We report the case of an 11.5-year-old boy who was referred to our hospital for evaluation of marked bilateral testicular enlargement in the previous few months. Physical examination revealed a testicular volume larger than 30 ml. Complementary investigations allowed us to rule out all hitherto reported etiologies of bilateral macroorchidism and therefore a diagnosis of idiopathic macroorchidism was established. The increased number of Sertoli cells found on biopsy, without elevated plasma FSH levels, prompted us to speculate about a hypothetical FSH receptor hyperfunction as a possible cause of the exaggerated testicular enlargement in this patient.

Assessment of interchangeability of two brands of levothyroxine preparations with a third-generation TSH assay

To evaluate, in a prospective fashion, the clinical interchangeability between two brands of levothyroxine, Synthroid (Boots Pharmaceuticals, Inc., Lincolnshire, Illinois) and Levoxine (Daniels Pharmaceuticals, Inc., St. Petersburg, Florida), by using clinical scores of hyperthyroidism and hypothyroidism, free thyroxine index (FTI), sensitive thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) stimulation testing. Twenty-three of the 31 patients with long-standing primary hypothyroidism (6 men, 25 women; age range 30 to 71 years, mean 47.2 +/- 2.2 SEM) were switched from Synthroid to Levoxine (group 1) and the remaining patients from Levoxine to Synthroid (group 2). After switching, each patient continued to receive the same dosage as previously. Clinical scores of hypothyroidism and hyperthyroidism (Billewicz and Crooks scoring systems, respectively), basal FTI, and TRH stimulation test were obtained before and 4 months after the switching. Comparison of the variables before and after switching was performed separately in each subgroup and in the entire group. There was no statistically significant difference in the hypothyroid clinical scores (-40.1 +/- 1.2 versus -39.7 +/- 1.2), the hyperthyroid clinical scores (-19.6 +/- 0.9 versus -19.2 +/- 1.0), FTI (9.6 +/- 0.3 versus 9.6 +/- 0.3), basal TSH levels (1.4 +/- 0.2 versus 1.4 +/- 0.2 mIU/L), or the magnitude of TSH response to TRH (mean delta TSH 9.4 +/- 1.5 versus 9.2 +/- 1.4 mIU/L), whether the patients were receiving Synthroid or Levoxine. Switching did not result in substantial clinical or laboratory changes in any individual patient. We conclude that the two brands of levothyroxine are clinically interchangeable.

Hypothalamic-pituitary gonadal axis in boys with primary hypothyroidism and macroorchidism

Nine of 15 boys with severe long-standing primary hypothyroidism were found to have macroorchidism. All 15 patients had elevated thyroid-stimulating hormone levels. However, only those patients with testicular enlargement had striking elevations of serum prolactin and gonadotropin values. The response to gonadotropin-releasing hormone in our patients was blunted, in contradistinction to that of children with true precocious puberty. In spite of the elevated levels of luteinizing hormone, the serum testosterone levels were in the prepubertal range, explaining the lack of peripheral manifestations of androgenic effect. Improvement of testosterone secretion followed decreasing prolactin levels with bromocriptine administration, suggesting an inhibitory effect of prolactin on luteinizing hormone action at the Leydig cell. We conclude that testicular enlargement is the result of continuous follicle-stimulating hormone stimulation and that the term "true precocious puberty" is not appropriate in children with hypothyroidism and macroorchidism unless the hypothalamic-pituitary gonadal axis is shown to be at the pubertal stage.

Transient growth hormone deficiency after treatment of primary hypothyroidism

In primary hypothyroidism, enlargement of the pituitary sella can mimic a primary pituitary tumor on computed tomography) Enlargement of the sella, thought to represent pituitary hyperplasia and hypertrophy in response to lack of feedback inhibition of thyroid hormone, has been demonstrated in 81% of adults with primary hypothyroidism. 2 The magnitude of the sellar enlargement is proportional to thyrotropin levels, and thyroid hormone replacement therapy can produce reduction of the enlarged pituitary gland to normal size. Rarely, treatment of primary hypothyroidism has resulted in hypopituitarism? A recent report documents by CT the development of an empty sella and hypopituitarism in a child after thyroid hormone replacement because of primary hypothyroidism. 4 Hypopituitarism in the absence of empty sella syndrome has also been described after thyroid hormone replacement. In only one reported patient, an adult with primary hypothyroidism, this hypopituitarism (gonadotropin deficiency) was thought to be transient? We report two children with longstanding primary hypothyroidism who grew poorly despite adequate hormone replacement and were found to have growth hormone deficiency. Subsequently, under androgen influence and without GH therapy, growth was good and testing showed adequacy of endogenous growth hormone secretion.

EFFECTS OF L-T4 THERAPY WITHDRAWAL ON GONADOTROPIN SERUM LEVELS IN L-T4 SUBSTITUTED HYPOTHYROID PATIENTS

Elevated serum LH levels and increased LH:FSH ratio which return to normal under L-T4 therapy are frequently observed in longstanding primary hypothyroidism and may account for the findings of precocious puberty and cystic ovaries in hypothyroids (Lindsay et al, Ai J Dis Child 134, 588, 1980). In 10 congenital hypothyroid subjects aged 7 to 18 yrs (6 prepubertal girls and 4 pubertal boys), L-T4 treatment was discontinued for a 3-week period in order to perform thyroid scan. All of them underwent iv LH-RH-test immediately before and 20 days after the therapy withdrawal. All the blood samples were processed in the same run. The shifting of TSH, T4 and T3 serum values froi the euthyroid to the hypothyroid range was accompanied in all the patients by a significant increase in both baseline LH (12.9±4.7 vs 6.3±2.5 mIU/ml, 2 p< 0.001) and PRL (22.6±11.7 vs 11.6±3.0 ng/ml, 2 p<0.05) plasia levels On the contrary LH peak after LHRH (22.5±7.9 vs 20.1±10.4) and either basal (2.4± ±1.5 vs 3.2± 2.1 mIU/ml) or stimulated (7.9±2.0 vs 6.8±2.0) FSH concentrations were not affected by L-T4 withdrawal. These results indicate that: a) an evident increase in LH serum levels precociously occurs in response to thyroid Failure; b) such increase does not reflect an enhanced sensitivity to LHRH; c) it may reflect anomalous LH reactivity to TRH (De Luca et al, Ped Res 18, 1222, 1984) or abnormal clearance (Lindsay et al).

Hyperprolactinemia and galactorrhea: spontaneous versus iatrogenic hypothyroidism.

Although hyperprolactinemia and galactorrhea occur in primary hypothyroidism, factors influencing their presence are not well established. To further define these factors, the duration of illness and serum levels of PRL and TSH were investigated in a group of 50 patients with spontaneous (27 females and 7 males) and iatrogenic (16 females) primary hypothyroidism. To test the hypothesis of reduced hypothalamic dopamine content in over long-standing primary hypothyroidism, the percent increase in serum PRL after the administration of metoclopramide, a dopamine blocker (2.5 mg, iv bolus), was studied in 13 women with spontaneous primary hypothyroidism and compared with that in 10 euthyroid women. While 88.2% of the patients with spontaneous primary hypothyroidism were hyperprolactinemia, only 31% of those with iatrogenic disease had elevated PRL levels. Women with spontaneous primary hypothyroidism had a longer duration of illness (72 +/- 12 vs. 6.7 +/- 1.8 months; P less than 0.001) and higher serum TSH (189 +/- 32 vs. 68 +/- 14 microunits/ml; P less than 0.01) and PRL levels (49.8 +/- 5.6 vs. 20.9 +/- 0.8 ng/ml; P less than 0.001) than women with iatrogenic hypothyroidism. A linear correlation existed between PRL and duration of illness (r = 0.53; P less than 0.001), while a logarithmic correlation was found between PRL and TSH levels (r = 0.44; P less than 0.01). Even though the duration of illness and TSH levels were similar in women with spontaneous disease with (n = 7) or without (n = 20) galactorrhea, the former were significantly younger (39.3 +/- 1.8 vs. 56.6 +/- 3 yr; P less than 0.001), and their PRL levels were significantly higher (69.3 +2- 8.9 vs. 42.9 +/- 2.2 ng/ml; P less than 0.001). The PRL response to metoclopramide in women with spontaneous disease was significantly smaller than that in controls (194 +/- 39% vs. 446 +/- 40%; P less than 0.001) and inversely correlated with basal PRL levels (r = -0.55; P less than 0.05). These data indicate that in primary hypothyroidism 1) the duration of illness is important in the development of hyperprolactinemia, 2) galactorrhea is more common in young women with spontaneous disease and high PRL levels, and 3) hypothalamic dopamine appears reduced in spontaneous disease.