Precocious puberty with congenital hypothyroidism

Precocious puberty associated with profound hypothyroidism is a rare condition. It is usually characterized by breast development, vaginal bleeding, lack of pubic hair and delayed bone age. Multicystic ovaries in profound hypothyroid patients with precocious puberty have been rarely described. Vaginal bleeding in adolescent girls should be considered as a clinical significance particularly when it is prolonged or heavy, whereas vaginal bleeding in younger girls, regardless of its duration and quantity is always of clinical importance. Bleeding in such patients could be caused by local causes such as vulvar or vaginal lesions, or it could be from the endometrium, which is usually a sign of systemic hormonal disturbance [1]. In this report a rare case of vaginal bleeding, large, multicystic ovaries, precocious puberty and delayed bone age in a 7 years old girl with profound hypothyroidism is described.     

Short stature and an interesting association

Untreated hypothyroidism in children usually results in delayed puberty, but juvenile hypothyroidism causes isosexual precocious puberty in a rare syndrome called Van Wyk Grumbach syndrome, with a complete reversal to the pre pubertal state following thyroid hormone replacement therapy. We report here, a 7-year-old girl who presented with short stature, constipation and isosexual precocious puberty due to the long standing untreated severe hypothyroidism with this syndrome.     

Osteopetrosis and Congenital Hypothyroidism Complicated by Slipped Capital Femoral Epiphysis

ObjectiveTo describe a 13-year-old girl with unilateral slipped capital femoral epiphysis (SCFE), who presented with an acute onset limp during follow-up for congenital hypothyroidism and osteopetrosis.MethodsWe present a case report detailing the patient’s history as well as clinical, laboratory, and imaging findings and discuss the related literature.ResultsThe patient had been diagnosed elsewhere with congenital hypothyroidism, and levothyroxine therapy was initiated when she was 20 days of age; however, adherence to the treatment was irregular. Both her weight and her height were below the 5th percentile, her breast development and pubic hair were consistent with Tanner stage 1, and she had mental retardation and atypical facies. Her gait was antalgic; no muscle atrophy or shortness in the affected leg was present. On laboratory investigation, thyroid function tests were concordant with primary hypothyroidism. Her bone age was estimated as 8 years. Dual-energy x-ray absorptiometry revealed increased bone mineral density. Radiographic studies disclosed striking opacity of the bones of the pelvis and sclerosis at the skull base. Computed tomography of the affected left lower limb showed a fragmented appearance of the capital femoral epiphysis and thickening and irregularities of the physis line on the left, consistent with SCFE.ConclusionWe underscore the possible facilitator role of osteopetrosis in the pathogenesis of SCFE, suggest the need to consider SCFE in the differential diagnosis when a lower extremity abnormality is detected in patients with congenital hypothyroidism or delayed puberty (or both), and emphasize this association with osteopetrosis.(Endocr Pract. 2010;16:646-649)     

Does Combination T4 And T3 Therapy Make Sense?

ObjectiveTo evaluate the existing evidence regarding the combined use of levothyroxine and liothyronine to treat hypothyroidism.MethodsEleven published randomized controlled trials evaluating the efficacy and safety of combined levo- thyroxine and liothyronine therapy for hypothyroidism were reviewed and summarized. Related basic and clinical research findings were also incorporated for perspective.ResultsAn initial randomized controlled trial reported symptomatic improvement in hypothyroid patients taking combined levothyroxine and liothyronine therapy compared with those taking levothyroxine therapy alone. Subsequently, multiple relatively small randomized controlled trials failed to demonstrate any subjective or objective benefit from combined levothyroxine and liothy- ronine therapy. A polymorphism (Thr92Ala) in the gene encoding the deiodinase 2 (D2) enzyme that converts thy- roxine to triiodothyronine in the brain was later identified in about 16% of hypothyroid persons. This polymorphism may impair brain deiodinase activity in the presence of low brain thyroxine levels. One randomized controlled trial found that patients with the D2 Thr92Ala polymorphism had more baseline symptoms than those with the wild type D2 and experienced significantly greater symptomatic improvement in response to combined levothyroxine and liothyronine therapy.ConclusionsMost hypothyroid patients experience rapid symptomatic relief after institution of levothyroxine replacement therapy, but persistent symptoms remain in some despite what appears to be adequate levothyroxine therapy with normalization of the serum thyrotropin level. A thorough investigation is warranted in these patients to detect and treat other responsible lifestyle issues, medical conditions, and endocrine conditions. A subset of hypo- thyroid patients has a polymorphism in the gene encoding the D2 enzyme that may prevent full resolution of symp- toms with levothyroxine therapy alone; these patients may benefit from combination levothyroxine and liothyronine therapy. (Endocr Pract. 2012;18:750-757)     

Reversibility of Fibrotic Appearance of Lungs with Thyroxine Replacement Therapy in Patients with Severe Hypothyroidism

ObjectiveTo present 2 cases of hypothyroidism with hypoxia associated with computed tomographic (CT) features suggestive of pulmonary fibrosis that resolved with correction of the hypothyroidism.MethodsClinical case histories are described, comparative radiologic pulmonary images before and after treatment are provided, and the pertinent literature regarding possible pathologic mechanisms is reviewed.ResultsOur first patient, a 68-year-old woman, presented with symptomatic severe hypothyroidism associated with respiratory failure. A CT scan of her lungs showed appearances suggestive of pulmonary fibrosis. Replacement therapy with levothyroxine led to correction of hypoxia and radiologic abnormalities. Our second patient, a 26-year-old man, presented with symptoms suggestive of obstructive sleep apnea that persisted despite use of positive pressure ventilation. Biochemical evaluation revealed severe hypothyroidism, and a CT scan disclosed pulmonary appearances consistent with fibrosis. His symptoms and radiologic abnormalities also improved after correction of hypothyroidism with levothyroxine therapy.ConclusionRadiologic pulmonary abnormalities suggestive of fibrotic disease are associated with severe hypothyroidism. Invasive investigations such as lung biopsy should be deferred until the clinical and radiologic responses to thyroxine replacement therapy have been assessed. (Endocr Pract. 2009;15:720-724)     

Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Mucocolpos In A Toddler: Central Precocious Puberty With Vaginal Atresia

ObjectiveTo report the first case of imperforate hymen and vaginal atresia in a patient with mucocolpos during toddlerhood who was found to have central preco cious puberty.MethodsWe review the details of assessment of an 18-month-old girl who had the presence of pubic hair and breast enlargement. She underwent biochemical evaluation with serum follicle-stimulating hormone, luteinizing hor mone, and estradiol and radiologic evaluation with ultra sonography of the abdomen and pelvis as well as magnetic resonance imaging of the pelvis and brain.ResultsThis young female patient had clinical and imaging findings suggestive of idiopathic central preco cious puberty. Imaging also revealed imperforate hymen, vaginal atresia, and mucocolpos. She underwent surgical treatment to ensure an unobstructed vaginal opening before initiation of gonadotropin-releasing hormone agonist ther apy, since the latter may precipitate uterine bleeding and might have converted mucocolpos to a combination of mucocolpos and hematocolpos.ConclusionThis case highlights the need to suspect the presence of precocious puberty in all female patients in whom mucocolpos is detected beyond infancy but before adolescence. (Endocr Pract. 2012;18:e144-e146)     

Precocious Puberty Due to Rathke Cleft Cyst in a Child

ObjectiveTo report a case of a child with precocious puberty attributable to Rathke cleft cyst (RCC).MethodsThe clinical features, laboratory results, and findings on ultrasonography of the pelvis and magnetic resonance imaging of the pituitary gland are presented.ResultsA 16-month-old child had breast enlargement, height increase, and an increase in growth velocity. On examination, she was found to have Tanner stage 3 breast development, and her vaginal mucosa was estrogenized. Her height was above the 97th percentile. Biochemically, she was diagnosed as having central precocious puberty, and magnetic resonance imaging of her pituitary gland disclosed RCC. Treatment with leuprolide resulted in normalization of her growth rate and regression of the breast development; the vaginal mucosa also became unestrogenized.ConclusionAlthough RCC is a relatively common finding, it is a rare cause of precocious puberty. Magnetic resonance imaging of the pituitary gland should be performed in all children younger than 6 years of age who have precocious puberty, in an effort to detect any organic lesions. (Endocr Pract. 2009;15:134-137)     

Effect of Proton Pump Inhibitors on Serum Thyroid-Stimulating Hormone Level in Euthyroid Patients Treated with Levothyroxine for Hypothyroidism

ObjectiveTo examine retrospectively the effect of proton pump inhibitors (PPIs) on thyrotropin (thyroid-stimulating hormone or TSH) values in patients with hypothyroidism and normal TSH levels receiving levothyroxine (LT₄) replacement therapy.MethodsThe data collection was done by retrospective review of electronic medical records from the period of December 2002 to August 2005 from patients with hypothyroidism who were receiving at least 25 μg of LT₄ replacement daily at Queens Hospital Center. The first 92 patients meeting all inclusion and exclusion criteria were included in the study. The study group (N = 37) patient data were collected by selecting euthyroid patients who had received stable LT₄ replacement for at least 6 months and in whom PPI therapy (lansoprazole) was later initiated. TSH levels were collected before and at least 2 months after the PPI treatment was started. The control group (N = 55) patient data were collected by reviewing TSH levels among euthyroid patients with a history of hypothyroidism receiving stable LT₄ therapy and not receiving a PPI during the period of data collection. The statistical analysis was done by comparing the mean change in TSH level in each group with use of the Student t test.ResultsIn the study group, the mean change in the TSH level from before to at least 2 months after initiation of PPI therapy, 0.69 ± 1.9 μIU/mL, was statistically significant (P = 0.035). In the control group, the mean change in the TSH level during the study period, 0.11 ± 1.06 μIU/mL, was not statistically significant (P = 0.45).ConclusionTo our best knowledge, this is the first study in humans with hypothyroidism demonstrating the effect of PPIs on serum TSH levels. PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT₄ replacement. Patients with hypothyroidism and normal TSH values during LT₄ replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT₄ dose. (Endocr Pract. 2007;13:345-349)     

Thyrotropin-Secreting Adenoma in a Patient with Primary Hypothyroidism

ObjectiveTo describe a patient who developed a thyrotropin (TSH)-Secreting adenoma in the setting of primary hypothyroidism.MethodsWe report the clinical, laboratory, and radiologic findings of a patient with a history of primary hypothyroidism who presented with headache, a bitemporal visual field deficit, and elevated TSH despite long-term levothyroxine therapy. We discuss the diagnostic challenges of this case and review the relevant literature.ResultsA54-year-old woman with a history of primary hypothyroidism presented with a 3-year history of headache and a week of worsening vision. Imaging revealed a heterogeneous sellar mass elevating the optic chiasm. Her serum TSH was 46.5 mIU/L and free thyroxine concentration was 0.1 ng/dL. The differential diagnosis included pituitary hyperplasia and a TSH-secreting adenoma in a patient with primary hypothyroidism. The pathologic characteristics of the tumor were consistent with the latter.ConclusionIn a patient with an elevated TSH concentration and a previous diagnosis of hypothyroidism, it is important to consider other entities besides medication noncompliance. TSH-secreting adenomas can also cause elevated levels of TSH. (Endocr Pract. 2011;17: e135-e139)     

A Rare Case of Central Precocious Puberty Due to Hypothalamic Hamartoma Diagnosed In Utero

ObjectiveTo report a rare case of central precocious puberty attributable to hypothalamic hamartoma that was diagnosed in utero.MethodsWe present the clinical, laboratory, and imaging data pertaining to our case and discuss the diagnostic features and recommended treatment of central precocious puberty in patients with hypothalamic hamartoma.ResultsA 3-month-old male child had had excessively rapid growth velocity and weight gain since birth. On investigation, the patient was diagnosed as having hypothalamic hamartoma with central precocious puberty. On inquiry, his mother described a history of prenatal ultrasonography and fetal magnetic resonance imaging suggesting the presence of a cystic lesion in his brain at 9 months of gestation. Because of continued rapid growth and acceleration of puberty during a 4-month observation period, we decided to treat the patient with leuprolide acetate. The patient responded well to treatment, with stabilization of growth.ConclusionTo the best of our knowledge, this patient is the youngest in the medical literature diagnosed to have central precocious puberty and also to receive treatment with leuprolide acetate. (Endocr Pract. 2010;16:237-240)     

Tyrosine Kinase Inhibitors and the Thyroid as Both an Unintended and an Intended Target

ObjectiveTo review the association of the tyrosine kinase inhibitor sunitinib with hypothyroidism as well as the mean time to onset, possible mechanisms, reversibility, and mean duration.MethodsWe performed a MEDLINE search of the English-language literature using a combination of words (“sunitinib,” “tyrosine kinase inhibitors,” “thyroid,” and “hypothyroidism”) to identify original studies and reviews on sunitinib and thyroid function.ResultsHypothyroidism was reported in 36% to 46% of patients who took sunitinib in prospective studies. A higher incidence (53% to 85%) was reported in studies containing both retrospective and prospective data. The mean time to onset of hypothyroidism after initiation of sunitinib therapy ranged from 12 to 50 weeks. The risk of development of hypothyroidism appears to increase with the increasing duration of sunitinib therapy, and the condition is likely reversible once therapy has been discontinued.ConclusionBaseline thyroid function tests should be performed before the initiation of sunitinib treatment. Because hypothyroidism can develop early in the course of therapy, thyroid function tests should be monitored frequently throughout the duration of treatment. Possible mechanisms for thyroid dysfunction include impaired thyroid hormone synthesis, a destructive thyroiditis preceding the development of hypothyroidism, and increased thyroid hormone clearance. If hypothyroidism is identified, levothyroxine therapy should be promptly initiated. (Endocr Pract. 2008;14:618-624)     

Chorea--an unusual manifestation in a woman recovering from myxedema coma

ObjectiveTo report a case of reversible chorea in a woman with myxedema coma.MethodsWe describe the clinical course, imaging findings, and laboratory test results of a patient who initially presented with myxedema coma and then developed reversible chorea upon treatment.ResultsA 33-year-old woman with a known history of primary hypothyroidism presented with a 3-week history of lethargy, progressing to a precipitous decline in consciousness that required intubation. Physical examination revealed concurrent hypothermia and bradycardia. Laboratory investigations demonstrated a thyrotropin concentration greater than 100 mIU/L, a free triiodothyronine concentration of 1.9 pg/mL, and a free thyroxine concentration of 0.24 ng/dL, but no other metabolic abnormalities. She was treated with intravenous levothyroxine therapy on the first 2 days of hospital admission (200 mcg and 250 mcg, respectively). On day 2, she was obeying commands and she was extubated. She began exhibiting choreiform movements. Thyroid function test results revealed a normal free thyroxine concentration (1.10 ng/dL), but an elevated thyrotropin concentration (40.98 mIU/L) and a low free triiodothyronine concentration (1.9 pg/mL). Findings from computed tomography and magnetic resonance imaging of her brain and analysis of cerebrospinal fluid were normal. Her regimen was transitioned to oral levothyroxine, 88 mcg daily, and by day 4, her choreiform movements ceased.ConclusionsNeurologic manifestations of hypothyroidism include psychomotor slowing, memory deficits, and dementia, with myxedema coma at the extreme of this spectrum. Although chorea is a rare manifestation of hyperthyroidism, this is the first report of a patient with acquired, reversible choreiform movement disorder while still being severely hypothyroid and treated with levothyroxine. (Endocr Pract. 2012;18:e43-e48)     

Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism

The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.     

Effect Of Levothyroxine Treatment On Qt Dispersion In Patients With Subclinical Hypothyroidism

ObjectiveTo examine the effect of levothyroxine treatment in patients with subclinical hypothyroidism on electrocardiographic variables, especially on ventricular repolarization-related factors.Methods:Sixteen women (mean age, 48.2 years) with subclinical hypothyroidism were treated with levothyroxine for 16 weeks. All standard 12-lead electrocardiograph-ic recordings were scanned and transferred to a computer, and the QT intervals were measured on 300 times magnified recordings. QT dispersion, which reflects the heterogeneity of the ventricular repolarization, was calculated by the difference between the QT maximum and the QT minimum.ResultsWe found that, after 16 weeks of levothyroxine treatment, the QT interval decreased from 387.2 ± 10.8 ms to 345.6 ± 13.0 ms (P < 40.0001). The study patients exhibited a significant reduction of QT dispersion from 46.5 ± 5.3 ms to 30.7 ± 5.8 ms (P < 0.0001). On linear regression analysis, a positive relationship was found between QT dispersion and logarithmic serum TSH levels (r = 0.492; P < 0.0001).ConclusionWe conclude that serum TSH concentration has a role in ventricular inhomogeneity and, therefore, that subclinical hypothyroidism may predispose to ventricular arrhythmias. A large-scale, multicenter, randomized trial should be undertaken to address the benefit-to-risk ratio of levothyroxine treatment on cardiac inhomogeneity in patients with subclinical hypothyroidism. (Endocr Pract. 2007;13:711-715)     

Levothyroxine Dosing in Older Adults: Recommendations Derived From The Baltimore Longitudinal Study of Aging

ObjectiveAs thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed.MethodsWe determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual.ResultsOne hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 μg/kg (1.35 μg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 μg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 μg/kg vs 1.14 μg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 μg/kg IBW; P = .41) compared with those with a body mass index of <30.ConclusionThyroid hormone dose per body weight estimates for replacement in older adults (1.09 μg/kg ABW or 1.35 μg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations.     

Urinary androgen response of 8 girls with precocious puberty given cyproterone acetate.

The effects of cyproterone acetate (CA), daily oral administration of 100 mg/m2, on the levels of urinary androgen excretion and velocity of skeletal maturation were studied in 8 girl patients with precocious puberty. Under therapy, testosterone excretion fell within a short time, and velocity of skeletal maturation normalized when the treatment was prolonged. Other beneficial effects such as stoppage of vaginal bleeding and no further growth of breast size and public hair, were also observed. Of 3 subjects, who were given CA for a period of 2--3 yrs, 2 showed further increments in testosterone excretion levels.     

Levothyroxine Pseudomalabsorption and Thyroxine Absorption Testing with Use of High-Dose Levothyroxine: Case Report and Discussion

ObjectiveTo report the case of a 55-year-old woman who had been prescribed a daily dose of 1, 000 μg of levothyroxine for the treatment of hypothyroidism but still had severe biochemical hypothyroidism and to discuss the use of thyroxine absorption testing to diagnose pseudomalabsorption.MethodsThe patient was admitted to the hospital for supervised thyroxine absorption testing. Baseline thyroid function tests were performed. An oral dose of 1, 000 μg of levothyroxine was administered while the patient had an empty stomach, and thyroid function tests were repeated at 2, 4, and 6 hours after administration. She was also given all her prescribed antihypertensive medications, and the blood pressure (which had been persistently high) was measured every 2 hours.ResultsAfter administration of 1, 000 μg of levothyroxine, a rapid improvement in the results of her thyroid function tests was noted. Similarly, a rapid decrease in her blood pressure was observed after supervised administration of her antihypertensive medications. A diagnosis of nonadherence to treatment (pseudomalabsorption of levothyroxine) was made. After reduction of her levothyroxine dosage to 100 μg daily, results of thyroid function tests showed improvement. The doses of her antihypertensive medications were likewise altered.ConclusionWe suggest that patients who are receiving doses of levothyroxine of more than 2 μg/kg of body weight, with persistently increased thyroid-stimulating hormone levels, should undergo testing for malabsorption and pseudomalabsorption of levothyroxine. Thyroxine absorption testing with use of high-dose levothyroxine is useful in diagnosing pseudomalabsorption but needs formal evaluation and validation. (Endocr Pract. 2010;16:1012-1015)     

Long-term suppression of pituitary-gonadal function with three-month depot of leuprorelin acetate in a girl with central precocious puberty

OBJECTIVE: The efficacy of a 3-month depot preparation of the GnRH agonist leuprorelin acetate in central precocious puberty was studied. METHODS: Treatment with a 3-month depot of leuprorelin acetate was performed subcutaneously in a 7.3-year-old girl with central precocious puberty. RESULTS: During treatment the hormonal suppression was constant and complete as demonstrated by suppressed GnRH stimulation tests and prepubertal estradiol plasma levels. The size and volume of the uterus and ovaries returned to the normal range. The rate of bone maturation was significantly reduced with a ratio deltaBA/deltaCA of 0.58 for 3 treatment years. Thus, the effects of treatment were comparable to those reported for treatment with 1-month depot of GnRH agonists. CONCLUSION: Three-month depots have the advantage of a prolonged injection interval which is more convenient for the patients and reduces costs by necessitating fewer visits to the physician and being approximately 10% cheaper than the 1-month depot. We suggest that comparative and randomized studies be performed to make 3-month depots of GnRH agonists available for routine use in children with central precocious puberty.     

Evaluation of Treatment of Central Hypothyroidism Versus Primary Hypothyroidism in Relation to Levothyroxine Replacement Dose

Objective: The aim of this study was to evaluate levothyroxine (LT4) replacement daily doses in patients with central hypothyroidism (CeH) and compare them with those adequate for patients with primary hypothyroidism (P-HYPO).Methods: We included 53 patients with CeH and 57 with P-HYPO, matched by sex, age, weight, and body mass index, in the period of 1 year. At the time of inclusion, all presented a stable and adequate dose of LT4 for at least 3 months, considering as adequate the dose associated with normal thyroid-stimulating hormone (TSH) levels and free thyroxine (T4) in P-HYPO patients, and free T4 levels in CeH patients.Results: The absolute daily dose of LT4 differed significantly between the two groups, 103.0 ± 27.1 μg (CeH) and 89.3 ± 32.0 μg (P-HYPO) (P = .017), even after adjustment for age, gender, and free T4 (P = .04). The LT4 dose adjusted to weight was also higher after adjustment for age, gender and free T4 (P = .04), with an average of 1.3 ± 0.4 μg/kg (CeH) and 1.2 ± 0.4 μg/kg (P-HYPO). Sheehan syndrome patients had a lower absolute daily dose of LT4 (P = .001), and patients who underwent pituitary radiotherapy required higher doses (P = .008). There was no difference in the daily dose of LT4 according to other pituitary hormone deficiencies.Conclusion: The results reinforce the relevance of a careful individualization of LT4 replacement in CeH management and the need for new markers for proper LT4 replacement therapy in such cases.Abbreviations: BMI = body mass index; CeH = central hypothyroidism; GH = growth hormone; LT4 = levothyroxine; P-HYPO = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone