Isolated ACTH deficiency accompanied by 'primary hypothyroidism' and hyperprolactinaemia

1983 ◽  
Vol 104 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Tadayoshi Yoshida ◽  
Tetsuya Arai ◽  
Jinpei Sugano ◽  
Hiroshi Yarita ◽  
Hideo Yanagisawa
Keyword(s):  
Pituitary Gland ◽  
Primary Hypothyroidism ◽  
Hormonal Changes ◽  
Plasma Acth ◽  
Isolated Acth Deficiency ◽  
Acth Deficiency ◽  
Corticotrophin Releasing Factor ◽  
Lysine Vasopressin ◽  
Before And After

Abstract. A 55 year old man with isolated ACTH deficiency is reported. The lesion would appear to be located in the pituitary gland since plasma ACTH and cortisol did not respond to lysine vasopressin and corticotrophin releasing factor (CRF). A fall in T4, a rise in basal values of TSH, prolactin (Prl), LH and FSH, excessive responses of TSH and Prl to TRH, and hyperreactive responses of LH and FSH to LRH were observed. These hormonal changes were examined before and after administration of cortisol. The abnormality in these hormones might be caused by deficiency of long-term glucocorticoid.

scholarly journals Persistence of hyperprolactinemia after treatment of primary hypothyroidism and withdrawal of long term use of estrogen: are the tuberoinfundibular dopaminergic neurons permanently lesioned?

2005 ◽  
Vol 49 (3) ◽  
pp. 468-472 ◽  
Author(s):  
Luiz Augusto Casulari ◽  
Fábio Celotti ◽  
Luciana A. Naves ◽  
Lucília Domingues ◽  
Carla Papadia
Keyword(s):  
Dopaminergic Neurons ◽  
Hormone Replacement ◽  
Hormonal Contraceptive ◽  
Primary Hypothyroidism ◽  
Trh Test ◽  
Pituitary Mass ◽  
Thyroid Hormone Replacement ◽  
Before And After ◽  
High Doses

Long term use of high doses of estrogen and the presence of chronic hyperprolactinemia may, at least in the rat, provoke lesions in the tuberoinfundibular dopaminergic (TIDA) neurons responsible for the control of prolactin (Prl) secretion. This occurrence, which is not yet well documented in humans, may have taken place in a patient on chronic oral hormonal contraceptive (OC) treatment who was seen for primary hypothyroidism, hyperprolactinemia and a pituitary mass. After thyroid hormone replacement, OC withdrawn and bromocriptine treatment, this patient could not maintain normal Prl levels, unless continuously treated with a dopaminergic agonist even when MRI was indicative of a normal situation. Function of TIDA neurons was investigated by TRH test (200µg IV) performed before and after treatment with 25mg carbidopa plus 250mg L-dopa every 4 hours for one day. Basal TSH was normal (3.9µU/mL) whereas basal Prl was high (67.5 ng/mL); both TSH and Prl levels appropriately increased after TRH: peaks 31.8µU/mL and 157.8 ng/mL, respectively. After treatment with carbidopa/L-dopa, basal TSH (1.6µU/mL) and Prl (34ng/mL) decreased and the response to TRH was partially blocked (10.3µU/mL and 61ng/mL, respectively). In spite of a normal response, we discuss the possibility that the persistence of hyperprolactinemia is due to lesion of the TIDA neurons produced by the long term use of high doses of estrogens and by the presence of chronic hyperprolactinemia.

Mechanism of restoration of ACTH release in rats with long-term lesions of the paraventricular nuclei

1986 ◽  
Vol 111 (1) ◽  
pp. 75-82 ◽  
Author(s):  
J. Dohanics ◽  
G. Kapócs ◽  
T. Janáky ◽  
J. Z. Kiss ◽  
G. Rappay ◽  
...  
Keyword(s):  
Median Eminence ◽  
Plasma Concentrations ◽  
Plasma Acth ◽  
Corticotrophin Releasing Factor ◽  
Paraventricular Nuclei ◽  
Basal Plasma ◽  
Corticosterone Response ◽  
Intact Rats ◽  
Acth Release

ABSTRACT The effects of lesions in the paraventricular nucleus (PVN) on the adrenocortical response to ether stress were investigated in neurohypophysectomized and intact rats. During the first 4 days after placement of lesions in the PVN, the corticosterone response to ether stress was almost completely inhibited. It then gradually increased and, within 4–6 weeks of surgery, was restored to about 60% of that in sham-operated rats. Basal plasma concentrations of corticosterone were low in rats after placement of lesions in the PVN and/or after neurointermediate lobectomy (NILX). Corticosterone responses to ether stress were similar in groups submitted to PVN lesions and/or NILX, and lower than those in the appropriate sham-operated groups. In all lesioned groups, plasma ACTH concentrations after a combination of stressors (ether plus laparotomy) were also lower than those in the sham-operated groups. Six weeks after lesioning of the PVN, immunoreactive rat corticotrophin-releasing factor-41 (rCRF-41) concentrations in stalk-median eminence (SME) extract fell to about 5% of that in sham-operated rats, while immunoreactive arginine vasopressin (AVP) concentrations did not change. Immunohistochemistry revealed a substantial decrease in rCRF-41 immunostaining of the median eminence 6 weeks after lesioning of the PVN, though randomly located clusters of stained terminals were still seen in the whole rostro-caudal extent of the median eminence. A mixture containing synthetic rCRF-41 and AVP, in proportions similar to those in SME extracts from sham-operated rats, caused significantly less release of ACTH from anterior pituitary cell cultures than did SME extracts from sham-operated rats. Extracts of SME from PVN-lesioned rats released as much ACTH as a mixture containing synthetic rCRF-41 and AVP in proportions similar to those in the SME extracts from PVN-lesioned rats. Extracts of SME from either PVN-lesioned or sham-operated rats did not cause a significant increase in the amount of ACTH released when preincubated with antisera to both rCRF-41 and AVP. It is suggested that (1) the restoration of the adrenocortical reponse to ether stress, evident within a few days of placement of lesions in the PVN, occurs independently of neurohypophysial function; (2) the full corticosterone and ACTH response to ether or ether plus laparotomy stress requires not only an intact PVN but also an intact neurointermediate lobe; (3) SME extracts from sham-operated rats contain a factor(s) with the ability to potentiate the ACTHreleasing effect of rCRF-41 and AVP; and (4) the ACTH-releasing activity of SME extract obtained from rats with long-term PVN lesions is probably due to its remaininJ content of rCRF-41 and AVP. J. Endocr. (1986) 111, 75–82

scholarly journals A Case of Isolated ACTH Deficiency Associated with Primary Hypothyroidism and GH Insufficiency

1997 ◽  
Vol 73 (3) ◽  
pp. 431-438
Author(s):  
Akira MATSUDA ◽  
Mutsuo BENIKO ◽  
Akemi IKOTA ◽  
Masao YAMAZAKI ◽  
Shigeki KOIZUMI ◽  
...  
Keyword(s):  
Primary Hypothyroidism ◽  
Isolated Acth Deficiency ◽  
Acth Deficiency

scholarly journals Missplicing due to a synonymous, T96= exonic substitution in the T-box transcription factor TBX19 resulting in isolated ACTH deficiency

2021 ◽  
Vol 2021 ◽  
Author(s):  
Ashwini Maudhoo ◽  
Avinaash Maharaj ◽  
Federica Buonocore ◽  
Gabriel Angel Martos-Moreno ◽  
Jesús Argente ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Serum Cortisol ◽  
List Type ◽  
Normal Range ◽  
Plasma Acth ◽  
Exon 2 ◽  
Isolated Acth Deficiency ◽  
Acth Deficiency ◽  
T Box

Summary Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 (also known as TPIT) is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD. We report a neonate of Romanian origin, who presented at 15 h of life with respiratory arrest and hypoglycaemia which recurred over the following 2 weeks. Biochemical investigations revealed IAD, with undetectable serum cortisol (cortisol < 1 μg/dL; normal range (NR): 7.8–26.2) and plasma ACTH levels within the normal range (22.1 pg/mL; NR: 4.7–48.8). He responded to hydrocortisone treatment. Patient DNA was analysed by a HaloPlex next-generation sequencing array targeting genes for adrenal insufficiency. A novel homozygous synonymous mutation p.Thr96= (Chr1:168260482; c.288G>A; rs376493164; allele frequency 1 × 10−5, no homozygous) was found in exon 2 of the TBX19 gene. The effect of this was assessed by an in vitro splicing assay, which revealed aberrant splicing of exon 2 giving rise to a mutant mRNA transcript whereas the WT vector spliced exon 2 normally. This was identified as the likely cause of IAD in the patient. The predicted protein product would be non-functional in keeping with the complete loss of cortisol production and early presentation in the patient. Learning points Synonymous variants (a nucleotide change that does not alter protein sequence) usually thought to be benign may still have detrimental effects on RNA and protein function causing disease. Hence, they should not be ignored, especially if very rare in public databases. In vitro splicing assays can be employed to characterise the consequence of intronic and exonic nucleotide gene changes that may alter splicing. Establishing a diagnosis due to a TBX19 mutation is important as it defines a condition of isolated ACTH deficiency not associated with additional pituitary deficiencies.

Effect of estradiol on the secretion of LH in the GnRH-pretreated rat after treatment with the GnRH-antagonist, Org 30093

1988 ◽  
Vol 119 (4) ◽  
pp. 582-588
Author(s):  
G. A. Schuiling ◽  
N. Valkhof ◽  
T. R. Koiter
Keyword(s):  
Pituitary Gland ◽  
Gnrh Antagonist ◽  
Plasma Concentrations ◽  
Estradiol Benzoate ◽  
The Other ◽  
Gnrh Analogue ◽  
Before And After ◽  
Pituitary Glands ◽  
Lh Secretion

Abstract. LH responses induced in the long-term ovariectomized rat by GnRH or GnRH agonistic analogue are augmented by E2. The augmentation by E2 does not occur during, but after termination of GnRH pretreatment. In this study it was investigated whether the augmenting effect of E2 develops also in the GnRH-pretreated rat when the animals were treated with GnRH antagonistic analogue. Two weeks after ovariectomy rats were treated for 10 days with 250 ng GnRH/h (GnRH-rats), released by sc implanted osmotic minipumps. Control rats received a Silastic 'sham pump'. Rats were simultaneously treated with solvent (oil) or estradiol benzoate (EB, 3 μg, sc). Each group of rats was divided into two subgroups, one receiving solvent, the other the GnRH antagonist, Org 30093 (ANT, 100 μg/injection) on 3 consecutive days. In Experiment 1, the pituitary LH content and the LH secretion following stimulation with the agonistic GnRH analogue buserelin, were measured, in Experiment 2, the plasma concentrations of LH before and after cessation of ANT treatment. The effects of treatment with GnRH, EB and ANT were studied on the basis of 1) the height of the maximal LH response and 2) the halfmaximally effective dose (ed 50) of buserelin. Experiment 1 revealed that GnRH depleted the pitutiary gland to about 42% of its original LH content. In EB-treated GnRH-rats the depletion was even stronger (to 14%). After ANT treatment, the pituitary glands of the GnRH-rats were (partly) repleted (oil: to 65%; EB: to 31%). ANT and EB had no effect on the pituitary LH content in control rats. EB increased the maximal LH response in control rats but not in GnRH-rats. ANT increased the maximal LH response to buserelin in oil-injected control rats as well as in oil- and EB-treated GnRH-rats. In these latter two groups, the increase of the maximal LH response was equally large. However, there was an effect of EB on the ed 50 of buserelin during ANT treatment, the pituitary gland of the EB-treated GnRH-rats had become more sensitive to GnRH. Experiment 2 revealed that GnRH pretreatment reduced the plasma LH concentrations to about 49% of the control levels. EB and ANT, too, lowered the plasma LH concentrations (to about 25%). Neither EB nor ANT, alone or in combination, changed the plasma LH concentrations in GnRH-rats. After cessation of ANT treatment, the plasma LH levels of the oil-injected control rats slowly returned to pretreatment levels, but those of the EB-treated control rats remained suppressed. In the GnRH-rats the reverse was seen: after cessation of ANT treatment, peaks of LH appeared in the plasma of the EB-treated rats, but not in the oil-injected. It is concluded that 1) treatment with ANT is not fully equivalent to termination of GnRH administration because it antagonizes the effects of GnRH only in part: 2) ANT has an intrinsic augmenting effect on the pituitary GnRH-responsiveness, and 3) owing to E2-induced sensitization of the pituitary gland, peaks of LH appear in the plasma of GnRH-rats but not of control rats after termination of ANT treatment.

scholarly journals Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Michael Y. Torchinsky ◽  
Robert Wineman ◽  
George W. Moll
Keyword(s):  
Severe Hypoglycemia ◽  
Hormone Deficiency ◽  
Published Data ◽  
Pituitary Hormone ◽  
Review Of The Literature ◽  
Older Children ◽  
Isolated Acth Deficiency ◽  
Acth Deficiency ◽  
Undetectable Plasma ◽  
Before And After

Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children is summarized. Review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in Prader-Willi syndrome. Isolated ACTH deficiency occurs in older children as well as in neonates.

Isolated ACTH deficiency due to long-term treatment with flunitrazepam

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
K Müssig ◽  
E Friess ◽  
K Mörike ◽  
HU Häring ◽  
D Overkamp
Keyword(s):  
Term Treatment ◽  
Isolated Acth Deficiency ◽  
Acth Deficiency ◽  
Long Term Treatment

CO-EXISTENT PRIMARY HYPOTHYROIDISM AND ISOLATED ACTH DEFICIENCY

1976 ◽  
Vol 82 (2) ◽  
pp. 467-474 ◽  
Author(s):  
T. Yamamoto ◽  
T. Ogihara ◽  
K. Miyai ◽  
Y. Kumahara ◽  
Y. Hirata
Keyword(s):  
Growth Hormone ◽  
Elevated Serum ◽  
Pituitary Hormones ◽  
Primary Hypothyroidism ◽  
Simultaneous Occurrence ◽  
Plasma Acth ◽  
Acth Deficiency ◽  
Thyrotrophic Hormone ◽  
Serum Thyroid Hormones

ABSTRACT A 52 year old man is described in whom the simultaneous occurrence of isolated adrenocorticotrophin (ACTH) deficiency and primary hypothyroidism was documented by the determination of six anterior pituitary hormones by specific radioimmunoassays after suitable stimulations. The urinary 17-hydroxycorticosteroids excretion was persistently reduced and was increased by repeated ACTH injections. The low basal metabolic rate, reduced serum thyroid hormones and elevated serum thyrotrophic hormone were consistent with primary hypothyroidism. After resumption of euthyroidism, secretory reserves of growth hormone and ACTH were assessed. The growth hormone response to insulin-induced hypoglycaemia was normal. No rise in plasma cortisol and ACTH was observed following insulin-induced hypoglycaemia. Plasma ACTH was not augmented by iv infusion of metyrapone. The pathogenesis of two co-existent endocrine deficiencies was discussed.

SOMATOTROPHIC AND CORTICOTROPHIC FUNCTIONS IN PRIMARY HYPOTHYROIDISM BEFORE AND AFTER THYROXINE TREATMENT

1973 ◽  
Vol 74 (3) ◽  
pp. 483-491 ◽  
Author(s):  
M. Minozzi ◽  
M. Faggiano ◽  
G. Lombardi ◽  
C. Carella ◽  
T. Criscuolo ◽  
...  
Keyword(s):  
Primary Hypothyroidism ◽  
Pituitary Function ◽  
Plasma Acth ◽  
Arginine Infusion ◽  
Hypothalamic Pituitary Adrenal ◽  
Thyroxine Treatment ◽  
Before And After ◽  
Pituitary Adrenal Axis ◽  
Different Levels ◽  
Multiple Interference

ABSTRACT In 12 patients with primary hypothyroidism the somatotrophic and corticotrophic functions were evaluated before and after thyroxine treatment. The results confirm a significant decrease, reversible by treatment, of plasma HGH responses to insulin-induced hypoglycaemia and to arginine infusion. Moreover, the results indicate that the impairment of the hypothalamic-pituitary function may also involve the response of plasma ACTH after provocative tests (insulin-induced hypoglycaemia and metyrapone). It must be stressed that the impairment of the corticotrophic function can be revealed only when the responses to provocative tests are evaluated by a direct assay of plasma ACTH and not by plasma corticosteroid modifications. These different responses may account for the conflicting results obtained by other investigators and may be justified by the multiple interference of the thyroid deficiency with the hypothalamic-pituitary-adrenal axis at different levels.

Influence of dopaminergic inhibition on serum levels of thyrotrophin and prolactin in patients with hypothyroidism before and after prolonged oral administration of TRH

1983 ◽  
Vol 104 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Harald M. M. Frey ◽  
Egil Haug
Keyword(s):  
Oral Administration ◽  
Serum Levels ◽  
Primary Hypothyroidism ◽  
Dopamine Antagonist ◽  
Trh Stimulation ◽  
Before And After ◽  
The Mean ◽  
Pre Treatment ◽  
Serum Tsh

Abstract. Forty mg TRH/day given orally for 3 weeks to 8 patients with mild primary hypothyroidism decreased serum TSH from a mean of 4.0 ng/ml ± 1.2 (se) to 2.0 ng/ml ± 0.4 (49%), and their mean incremental TSH response to iv TRH was equally reduced from 8.6 ng/ml ± 2.5 to 4.0 ng/ml ± 1.9 (46%). In the same patients serum Prl was 8.2 ng/ml ± 2.2 before oral TRH treatment and 6.6 ng/ml ± 1.5 (81%) after treatment, and the mean incremetal Prl response to iv TRH was reduced from 43.5 ng/ml ± 5.0 to 35.9 ng/ml ± 7.5(83%). The oral administration of 10 mg of the dopamine antagonist metoclopramide increased mean serum TSH from 0.6 ng/ml ± 0.1 (se) to 0.7 ng/ml ± 0.1 (120%) in euthyroid subjects and from 4.0 ng/ml ±1.2 to 5.7 ng/ml ± 1.6 (145%) in patients with primary hypothyroidism, and mean serum Prl from 8.6 ng/ml ± 0.8 to 109.5 ng/ml ± 24.3 (1251%) and from 8.2 ng/ml ± 2.2 to 119.6 ng/ml ± 45.5(1460%), respectively. The incremental TSH responses to iv TRH increased 2.3-fold in euthyroid subjects pre-treated with metoclopramide, while no change was observed in the TSH responsiveness in patients with primary hypothyroidism following metoclopramide pre-treatment. In the euthyroid subjects metoclopramide treatment had no effect on the Prl response to iv TRH. In the primary hypothyroid group metoclopramide pre-treatment caused a reduced Prl response to iv TRH in more than 50% of the patients. It is concluded that long-term TRH treatment decreased the serum levels of TSH and Prl as well as the incremental increases in TSH and Prl to iv TRH stimulation in patients with primary hypothyroidism. Long-term TRH treatment did not change the TSH and Prl responses to the dopamine antagonist metoclopramide.

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