The term primary empty sella (PES) makes reference to the herniation of the subarachnoid space within the sella turcica in patients with no history of pituitary tumor, surgery or radiotherapy. To ...retrospectively assess clinical features, radiological findings and the biochemical endocrine function from the records of 175 patients with a diagnosis of PES. One hundred seventy-five patients (150 females) were studied. The mean age at diagnosis was 48.2 ± 14 year. Most diagnoses were made by magnetic resonance imaging (n = 172). In most patients, the pituitary function was assessed by basal pituitary hormones measurements. Pituitary scans were ordered for different reasons: headache (33.1 %), endocrine disorders (30.6 %), neurological symptoms (12.5 %), visual disturbances (8.75 %), abnormalities on sella turcica radiograph (8.75 %) and others (6.25 %). Multiple pregnancies were observed in 58.3 % of women; headaches, obesity, and hypertension were found in 59.4, 49.5, and 27.3 % of the studied population, respectively. Mild hyperprolactinemia (<50 ng/ml) was present in 11.6 % of women and 17.3 % of men. Twenty-eight percent of our patients had some degree of hypopituitarism. In the male population, hypopituitarism represented 64 % of cases, whereas it accounted for 22 % of all females. PES seems to be more commonly found in middle-aged women, with a history of multiple pregnancies. In most patients, PES was discovered as an incidental finding on imaging studies, while in almost a quarter of patients PES was found during the diagnostic evaluation of anterior pituitary deficiency, which was more common in men.
Summary
Context
Acromegaly is characterized by GH excess and insulin resistance. It is not known which of these disorders is responsible for the increased atherogenic risk in these patients.
...Objective
To analyse the associations of GH and homoeostasis model assessment (HOMA) with biomarkers of cardiovascular disease and to compare the above‐mentioned variables between patients with active acromegaly and controls.
Design and setting
This open cross‐sectional study was conducted at a University Hospital.
Patients
Twenty‐two outpatients were compared with sex‐ and age‐matched control subjects.
Main outcomes
Included clinical features, hormonal status, markers of insulin resistance, lipoprotein profile and biomarkers of cardiovascular disease.
Results
Patients presented higher triglyceride (median IQR) (1·21·1–1·6 vs 0·90·6–1·1 mm, P < 0·05), low‐density lipoprotein‐cholesterol (LDL‐C) (mean ± SD) (3·5 ± 0·9 vs 3·0 ± 0·7mm, P < 0·05), apoB (0·98 ± 0·23 vs 0·77 ± 0·22 g/l, P < 0·05), free fatty acid (0·69 ± 0·2 vs 0·54 ± 0·2 mM, P < 0·05), oxidized‐LDL (120 ± 22 vs 85 ± 19 U/l, P < 0·05) and endothelin‐1 (0·90 ± 0·23 vs 0·72 ± 0·17 ng/l, P < 0·05) levels, increased cholesteryl ester transfer protein (CETP) activity (179 ± 27 vs 138 ± 30%/ml/h, P < 0·01) and lower C reactive protein (CRP) (0·250·1–0·9 vs 0·850·4–1·4 mg/l; P < 0·05) levels than control subjects. Vascular cell adhesion molecule (VCAM‐1) concentration was not different. By multiple linear regression analyses, HOMA explained the variability of triglycerides (25%), high‐density lipoprotein‐cholesterol (HDL‐C) (30%) and CETP activity (28%), while GH independently predicted LDL‐C (18%), oxidized‐LDL (40%) and endothelin‐1 levels (19%).
Conclusions
In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro‐oxidative and pro‐inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL‐C, ox‐LDL and endothelin‐1.
Purpose
Disorders of the hypothalamic-pituitary-thyroid axis are common in patients with acromegaly and thyroid enlargement is present in the majority of them. The exact prevalence of goiter in ...patients with acromegaly remains uncertain and the presence of thyroid autoimmunity has not been extensively evaluated so far.
Methods
We retrospectively evaluated thyroid biochemical and morphological findings in 116 acromegalic patients who attended our hospital. Serum TSH, total thyroxine levels and anti-thyroid peroxidase (ATPO) antibodies were measured by standard ultrasensitive techniques in all the patients. Thyroid ultrasound was performed in 75 out of them. The antibody control group was composed by healthy Argentinean individuals who attended the blood bank of our hospital in whom ATPO antibodies were measured.
Results
Twenty-nine out of the 116 acromegalic patients (25 %) showed elevated titers of thyroid antibodies (79 % were women and 21 % men). The control group had a 10 % prevalence of thyroid autoimmunity. The prevalence of goiter by ultrasound was 36 %, being more common in females (41 %) than in males (28 %). Thirty-five percent of patients who presented thyroid nodules and 44 % of patients with ultrasound diagnosed goiters had positive thyroid autoimmunity. There was no significant correlation between the presence of nodules and IGF-1 levels, duration of disease or age.
Conclusion
We found a high prevalence of thyroid autoimmunity in our patients with acromegaly as compared to the normal population. Thyroid autoimmunity seems to be an additional mechanism for the development of thyroid disorders in acromegaly.
Summary
Objective Active acromegaly is associated with increased mortality from cardiovascular causes. Several studies have shown increased atherogenic risk factors and biomarkers of inflammation ...and atherosclerosis in association with growth hormone excess. The aim of this study was to evaluate oxidized low density lipoprotein (oxLDL) levels and some modulators of LDL oxidative modification in patients with acromegaly.
Design Open transversal study.
Patients Fifteen patients with active acromegaly and 15 controls were studied.
Measurements We evaluated the levels of oxLDL, thiobarbituric acid reactive substances (TBARS), ceruloplasmin, bilirubin, uric acid and total reactive antioxidant potential, and the activities of ceruloplasmin, myeloperoxidase, superoxide distmutase, paraoxonase 1, and platelet activating factor acethylhydrolase. Statistical analysis was performed including body mass index as a covariate or as a fixed variable.
Results Patients with acromegaly showed significantly higher levels of oxLDL (120 ± 19 vs. 86 ± 20 U/l, P < 0·001) and endothelin (P < 0·05), increased ceruloplasmin activity (P < 0·01) and a trend towards higher values in TBARS concentration (P = 0·07) in comparison to healthy controls. OxLDL was positively associated with GH, IGF‐I and its binding protein 3 (r = 0·63, P < 0·001; r = 0·53, P < 0·01; and r = 0·56, P < 0·01; respectively). OxLDL showed direct associations with endothelin‐1 (r = 0·53, P < 0·01) and ceruloplasmin activity (r = 0·43, P < 0·05). The other parameters evaluated were similar in both groups.
Conclusions The increase in plasma oxLDL levels, a direct marker of the plaque formation, could constitute a link between atherosclerosis and active acromegaly. LDL oxidation would not be the consequence of diminished antioxidant defences, but of an enhancement in prooxidant factors like ceruloplasmin.
Summary
Objectives In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. ...Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex‐ and age‐matched healthy controls.
Patients Eighteen patients with active acromegaly and 18 controls were studied.
Measurements Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) were measured by radiometric techniques, endothelin‐1 and vascular cell adhesion molecule (VCAM)‐1 by enzyme‐linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry.
Results After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 ± 17 vs. 141 ± 30% per ml h, respectively; P < 0·05). Endothelin‐1 levels evidenced an increase in the patients’ group (0·9 ± 0·2 vs. 0·7 ± 0·2 ng/l, respectively; P < 0·01) and showed positive and significant correlations with GH, IGF‐1 and IGFBP‐3 (r = 0·45, 0·42 and 0·44, respectively; P < 0·01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 ± 59 vs. 246 ± 48 arbitrary units, respectively; P < 0·05).
Conclusions Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.
Alterations of the gene encoding the pituitary transcription factor
PROP1 were associated with congenital forms of multiple pituitary
hormone deficiencies in several families. Among 23 patients with
...multiple pituitary hormone deficiencies screened for a
PROP1 gene abnormality, nine belonging to eight
unrelated families had homozygous PROP1 gene defects.
All mutations were located in exon 2 and affected only two different
sites: a homozygous AG deletion at codons 99/100/101 (n = 5);
homozygous point mutations affecting codon 73: R73C (n = 2) or
R73H (n = 1), and a R73C/R99X double-heterozygous mutation (n=
1). R73H and R99X were never described. All patients were born to
unaffected parents, and consanguinity was documented in two patients.
They had complete GH, LH-FSH, and TSH deficiencies and normal basal
levels of PRL. Delayed ACTH deficiency was diagnosed in four of nine
patients. At magnetic resonance imaging the anterior pituitary was
hypoplastic in seven patients and hyperplastic in two. This study found
two novel mutations (R73H and R99X) and underlines the high incidence
of PROP1 gene alterations in patients with multiple
pituitary hormone deficiencies. A corticotroph deficiency was
frequently observed in association with GH, TSH, and gonadotropin
deficiencies and should be carefully sought during follow-up.
To report the management and outcome of three cases of papillary carcinoma (PC) in thyroglossal duct cysts (TGCs).
We present case reports of one female and two male patients between the ages of 22 ...and 46 years who had TGCs. In addition, we discuss the theories about the pathogenesis of TGC carcinoma (de novo versus metastatic lesions).
In all three patients, we found a TGC that contained a vegetating mass. Subsequent pathologic examination revealed the presence of a PC. All patients underwent total thyroidectomy, and two of them concurrently had PC in the thyroid gland. Besides the PC in the TGC, the first patient had a "cold" scintigraphic thyroid nodule that was also a PC, whereas the second patient had a thyroid microcarcinoma that had not been detected before surgical intervention. The third patient did not have carcinoma of the thyroid, but the histologic pattern of the gland resembled that observed in de Quervain's disease. We interpreted this finding as "palpation thyroiditis." The patients received postoperative 131I and suppressive therapy with levothyroxine. During a follow-up period of 2 to 12 years (mean, 5.8), we found no recurrence of the disease, and serum thyroglobulin remained undetectable in all cases.
Although use of total thyroidectomy followed by radioiodine therapy and suppressive treatment with levothyroxine is a matter of debate in patients with PC in TGCs, we conclude that this approach yields a favorable outcome in most cases, especially when the thyroid is also involved by the PC, and allows a better postoperative follow-up.
The GH receptor antagonist pegvisomant is an efficient agent to achieve biochemical control of acromegaly in those cases refractory to surgery and medical therapy with somatostatin analogs. We ...conducted an observational multicenter study consisting of data collection in accordance with the standard management of patients with acromegaly in everyday practice. We reviewed the medical records of 28 patients, 23 females, who were treated with pegvisomant due to the lack of biochemical response or intolerance to the somatostatin analogs. The objective was to monitor long-term safety and efficacy of the antagonist. 82% of the patients had previous pituitary surgery, 53.6% radiotherapy and 96.4% received medical therapy for acromegaly. Only 19.2% of the patients had pituitary residual tumor size larger than 1 cm, the remainder harbored a microadenoma or no visible tumor in the pituitary images. In terms of biochemical efficacy, IGF-I levels decreased to normal ranges in 45% and 58.8% of patients after 3 and 6 months of treatment, respectively, the daily mean dose of pegvisomant being 9.6+/-1.1 mg. Adverse events, potentially related to pegvisomant were reported in 6 patients (21.4%), local injection site reaction and elevated liver enzymes being the most frequent. Tumor size did not show enlargement in the evaluated population (15 patients) during the period of the study. This paper presents preliminary data from a small observational study in Argentina which represents the first database in our country.
El tirotropinoma es el adenoma hipofisario menos frecuente (< 2 %). Debido a su infrecuencia, describimos 5 casos. Caso 1: Varón de 23 años, presentó fibrilación auricular aguda. El perfil tiroideo ...mostró: TSH: 4,2 uUI/ml (0,3-4), T4: 14,8 ug/dl (4,5-12,5), T4L: 2,2 ng/dl (0,8-1,9),T3: 170 ng/dl (80-180), T3L: 7,8 pg/ml (1,8-4,6) y test de TRH-TSH plano. La resonancia nuclear magnética (RNM) de cerebro reveló un macroadenoma. Se inició tratamiento con metimazol sin lograr respuesta apropiada. Luego comenzó tratamiento con octreótido-Lar logrando el eutiroidismo. Fue intervenido por vía transesfenoidal (TE), confirmándose por inmunohistoquímica (IHQ) adenoma (+) para TSH. A los 7 días luego de la cirugía la TSH se constató suprimida. Cinco años después se encuentra en remisión. Caso 2: Mujer de 41 años, consultó por hipertiroidismo bioquímico e hipertensión arterial (HTA). La evaluación hormonal mostró: TSH: 3,21 uUI/ml (0,4-4), T4: 16,9 ug/dl (4,5-10,9), T4L: 2,2 ng/dl (0,8-1,5), T3: 245 ng/dl (60-180) y test de TRH-TSH plano. La RNM evidenció un microadenoma de 2 mm. La terapia con cabergolina no modificó las hormonas tiroideas. El tumor mostró crecimiento progresivo (10,8 mm a los 2 años). Se operó por vía TE y el tumor fue (+) en la IHQ para TSH y GH. Luego de la cirugía presentó TSH suprimida por 15 días. Actualmente lleva un año y medio libre de enfermedad. Caso 3: Hombre de 53 años consultó por disminución de la libido, impotencia sexual y aumento de peso. El laboratorio reveló: TSH: 9,1 uUI/ml, T4L: 1,79 ng/dl (0,9-1,8), T3: 164 ng/dl (40-181). En la RNM se halló un macroadenoma. Se realizó cirugía TE, el adenoma fue (+) para TSH y GH en la IHQ. Evolucionó con hipotiroidismo primario. Caso 4: Mujer de 36 años consultó por hipertiroidismo. El perfil tiroideo reveló: TSH: 3,76 uUI/ml (0,4-4), T4: 13,2 ug/dl (4-12), T4L: 2,3 ng/dl (0,9-1,7), T3: 247 ng/dl (70-200) y test TRH-TSH plano. La RNM evidenció un adenoma de 10 mm. Se intervino por vía TE. La IHQ fue (+) para TSH y GH. Evolucionó con TSH suprimida hasta los 15 días y el último perfil tiroideo a los 8 años fue normal. Caso 5: Hombre de 49 años consultó por disminución de la libido y cefaleas ocasionales. El laboratorio mostró: TSH: 14,4 uUI/ml (0,3-4,9), T4: 14,8 ug/dl (4,5-12), T4L: 4,1 ng/dl (0,8-1,5). La RNM mostró un macroadenoma invasivo. Inició tratamiento con octreótido-Lar y se perdió en el seguimiento. Conclusiones: Presentamos estos casos debido a su baja prevalencia. Destacamos que la presentación clínica fue variable. En los casos oligosintomáticos para hipertiroidismo, podría especularse con una secreción TSH tumoral con menor actividad biológica. Los cinco pacientes presentaron TSH no suprimida. Tres, tuvieron macrodenoma al momento del diagnóstico. En tres casos se constató TSH suprimida a la semana de la cirugía pudiendo considerar este dato como un criterio de curación. Los cuatro pacientes operados curaron con la cirugía. Rev Argent Endocrinol Metab 51:141-150, 2014 Los autores declaran no poseer conflictos de interés
Alterations of the gene encoding the pituitary transcription factor PROP1 were associated with congenital forms of multiple pituitary hormone deficiencies in several families. Among 23 patients with ...multiple pituitary hormone deficiencies screened for a PROP1 gene abnormality, nine belonging to eight unrelated families had homozygous PROP1 gene defects. All mutations were located in exon 2 and affected only two different sites: a homozygous AG deletion at codons 99/100/101 (n = 5); homozygous point mutations affecting codon 73: R73C (n = 2) or R73H (n = 1), and a R73C/R99X double-heterozygous mutation (n = 1). R73H and R99X were never described. All patients were born to unaffected parents, and consanguinity was documented in two patients. They had complete GH, LH-FSH, and TSH deficiencies and normal basal levels of PRL. Delayed ACTH deficiency was diagnosed in four of nine patients. At magnetic resonance imaging the anterior pituitary was hypoplastic in seven patients and hyperplastic in two. This study found two novel mutations (R73H and R99X) and underlines the high incidence of PROP1 gene alterations in patients with multiple pituitary hormone deficiencies. A corticotroph deficiency was frequently observed in association with GH, TSH, and gonadotropin deficiencies and should be carefully sought during follow-up.
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