Clinical Endocrinology (1976) 5, 145-150.
CASE O F H Y P E R T H Y R O I D I S M D U E TO A CHROMOPHOBE A D E N O M A * P. H . B A Y L I S
Department of Medicine, Queen Elizabeth Hospital, Birmingham
(Acceptedfor publication 9 September 1975)
SUMMARY
A 23-year-old man with secondary hypogonadism was also found to be thyrotoxic. Results of thyroid function tests were in the hyperthyroid range but the serum TSH was inappropriately high. A pituitary tumour was demonstrated and following hypophysectomy he became biochemically hypothyroid. Evidence is presented and discussed that his hyperthyroidism was due to excessive TSH production by the pituitary tumour. Hyperthyroidism is usually associated with immeasurably low serum thyroid stimulating hormone (TSH) concentrations. However, seven cases have now been reported in which excessive TSH production by the pituitary gland has been demonstrated, in two cases by bioassay (Jailer & Holub, 1960; Lamberg et al., 1969) and in five by radioimmunoassay (Hamilton et al., 1970; Faglia et al., 1972; O’Donnell et al., 1973; Emerson & Utiger, 1972). A further patient is described below who had hyperthyroidism due to excessive TSH production by a chromophobe adenoma. CASE HISTORY A 23-year-old male agricultural student was admitted to the Queen Elizabeth Hospital, Birmingham, in January 1974 for investigation of weight loss, lack of energy and loss of body hair since October 1972. He subsequently developed episodes of irritability associated with mild heat intolerance. Physical examination revealed a pale, smooth-skinned young man, height 181 cm and weight 65 kg. He had sparse axillary, facial and pubic hair. His thyroid gland was slightly enlarged but there was no associated bruit. Exophthalmos and lid-lag were not demonstrated. The testes were small. His pulse rate was 100/min, and there was marked proximal muscle weakness. Initial investigations confirmed the clinical suspicion of hyperthyroidism (Table 1).
* Presented at The Royal Society of Medicine, Endocrine Section, on 27 November 1974. Correspondence: Dr P. H . Baylis, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH.
145
P. H. Baylis Thyroid scan was normal and thyroid antibodies were not found in the serum. A surprising result, in the face of hyperthyroidism, was a measurable serum TSH concentration of 5 mu/l (normal range 0-5 mu/l). The TSH concentration in the same sample was kindly measured by Dr H. Schleusner in Berlin and Dr F. Maloof in Boston, U.S.A.,both of whom found elevated levels (Table 1). Dr Maloof also measured alpha and beta subunits of TSH, both of which were not raised. TABLE1. Results of endocrine studies on presentation in January 1974 Patient Protein bound iodine (PBI) (pgldl) Serum thyroxine (T4) (pg/dl) Serum triiodothyronine (T3) fngfdl) T3 uptake test (%) Serum cholesterol (mg/dl) Basal TSH Dr Butt, Birmingham (mu/]) Dr Schleusner, Berlin (mu/l) Dr Maloof, Boston (pu/ml) TSH subunits: a-subunit (nglml) B-subunit (ng/ml) 13'1 uptake at 24 h (%) After T3 suppression (%) Thyroid antibodies Long acting thyroid stimulator (LATS) activity Long acting thyroid stimulator protector (LATSP) activity Urinary 17 oxosteroids (pmo1/24 h) Urinary 17 oxogenic steroids (pmo1/24 h) Serum testosterone (nmol/l) Serum total androgens (nmol/l) Plasma cortisol at 09.00 hours (nmol/l) Urinary free cortisol (nmo1/24 h) Basal prolactin (nglml) Basal growth hormone (mu/l) (no response to hypoglycaemia) Basal luteinizing hormone (LH) (u/l) Basal follicle stimulating hormone (FSH) (u/l) (no response to LHRH)
8.0 11.2 273 91 147 5
Normal 3'5-8.0 43-1 1.0 122-240 90-1 17 136-280
0-5 0.8-6.0 0-3'5
16.2 4.5 1.1 0.5 91.4 33.0 Negative
20-45 20-45 Negative
Negative
Negative
Negative 30 58 0.6 2.0 121 180 73 1
Negative 7-70 10-80 10-40 15-48 140-700 30-420 40 0-25
4 2
-
2-8 1-7
The serum total androgens were low (2-0 nmol/l), but adrenal function was satisfactory (urinary free cortisol 180 nmo1/24 h). Skull X-ray showed an enlarged pituitary fossa with erosion of the internal walls and a double contour to the floor. An air encephalogram showed no suprasellar extension. Basal serum TSH concentration was 5 mu/l and failed to rise after 200 pg of intravenous thyrotrophin releasing hormone. Serum prolactin was elevated and failed to increase further after TRH. Results of other relevant pituitary function tests are shown in Table 1. Perimetry of the visual fields was normal.
Hyperthyroidism due to a chromophobe adenoma
147
He was started on Carbimazole in February and within 2 months his thyrotoxicosis had improved clinically and biochemically (Fig. 1). On 1 May 1974 a transphenoidal hypophysectomy was performed by Mr G . A. Dalton. A large cystic tumour was removed, the histology of which revealed a chromophobe adenoma. He made an uneventful post-operative recovery and cortisone acetate replacement was started. He was thereafter seqn regularly in the Outpatients Department, where return of his secondary sexual features was noted. I
Hypophysectomy
- 5 mg 3 x 1 2 4 h I
Z"P
"-
.-
1 I2O 00
f
sol
-
1
-I
1
I
I
I
I
'
I
I
I
I
'
Months
FIG.1. Serial estimations of thyroxine, triiodothyronine, T3 uptake test and thyroid stimulating hormone from January 1974.
At the end of August 1974 he was readmitted for further assessment. His improved gonadal function was confirmed biochemically (total androgens 24 nmol/l). The thyroid function tests were mildly hypothyroid (serum T4 4.2 pg/dl, serum T3 70 ng/dl, T3 uptake test 107%) while the TSH level which had been almost undetectable immediately after surgery had returned to 5 mu/l and rose to 8 mu/l at 30 and 60 min after 200 p g TRH. The radioactive iodine uptake test returned to normal (30.6% at 24 h). There was a slight response of serum LH and FSH to LHRH, but no response of cortisol or growth hormone to insulin-induced hypoglycaemia. Basal serum prolactin was now in the normal range, and rose to 60 ng/ml after 200 pg TRH.
148
P.H. Baylis DISCUSSION
This young man presented with symptoms of hypogonadism shown to be due to a chromophobe adenoma of the pituitary gland. Clinically, hyperthyroidism was postulated to account for his marked weight loss, sweating, anxiety and tachycardia. A free thyroxine index based on serum PBI or serum T4 concentration combined with a T3 uptake test was definitely in the hyperthyroid range; serum T3 concentration was high and thyroidal uptake of l 3 'I was markedly elevated. These features seemed to confirm the presence of hyperthyroidism, which was further supported by his clinical and laboratory response to carbimazole. Two features militated against this diagnosis : measurable serum TSH concentration above our normal radioimmunoassay range, which was supported by D r Schleusner and Dr Maloof, and suppression of his thyroidal l 3'I uptake by triiodothyronine. Coincidental coexistence of hyperthyroidism and hypopituitarism would appear questionable from these findings, unless pituitary gland secretion of TSH was itself responsible for the hyperthyroidism. In this case, by anology with some benign adrenal tumours, incomplete suppression of thyroidal activity by triiodothyronine might be anticipated. Repeated TRH stimulation of the pituitary consistently showed no rise in the serum TSH concentration above the elevated basal levels; thus implying at least some suppression of the pituitary by circulating thyroid hormone. The failure of a rise in TSH following TRH is consistent with the diagnosis of hyperthyroidism. However, thyroidal l3 'I uptake was suppressed by triiodothyronine which is most unusual in hyperthyroidism and this probably indicates that the excessive TSH production was not autonomous. His skull X-ray suggested a pituitary tumour which was the most likely site of inappropriate TSH production. The pituitary origin of his hyperthyroidism was supported further by his clinical response to hypophysectomy, after which he became mildly hypothyroid with the serum TSH becoming undetectable. This later rose to its former level as he became euthyroid. Furthermore, following hypophysectomy his previously elevated serum prolactin levels returned to normal and showed a normal response to intravenous TRH, which may, in part, explain the return of hair growth and sexual activity. In this patient other possible causes of hyperthyroidism seemed unlikely. At no stage were there any clinical features of Graves' disease and neither LATS nor LATS protector activities were demonstrated (Adams & Kennedy, 1967; Adams et al., 1974). Non-suppression of thyroidal uptake of 13'1 by triiodothyronine is almost a sine qua non of Graves' disease or hyperthyroidism due to a toxic adenoma or multinodular goitre. This patient's thyroidal uptake suppressed dramatically indicating that the excessive thyroxine production was not autonomous. Hyperthyroidism associated with elevated serum TSH levels has been recorded in patients suffering from malignant disease including testicular carcinoma, hydatidiform mole and chorion-carcinoma, but no such disease was demonstrated in this patient (Steibigel et al., 1964; Hershman & Higgins, 1971). It was therefore concluded that this patient's hyperthyroidism was due to excessive TSH production by a chromophobe adenoma of the pituitary gland. Until 1960 there appear to have been eight cases reported of hyperthyroidism associated with chromophobe adenoma (Nurnberger & Korey, 1953; Werner & Stewart, 1958; Kappeler, 1959; Nyhan & Green, 1964; Jackson, 1965; Maurer et al., 1966). It had been presumed that these tumours had secreted excess TSH. In 1960, Jailer & Holub reported the
Hyperthyroidism due to a chromophobe adenoma
149
first case of hyperthyroidism and pituitary tumour in which the serum TSH was elevated, as measured by the bioassay technique of D’Angelo et al. (1951). In 1969 Lamberg et al., using a different bioassay (McKenzie, 1958), reported a patient with a chromophobe adenoma, acromegaly, hyperthyroidism and hyperparathyroidism. Since then radioimmunoassay of TSH (Ode11 et al., 1967) has been established and four further cases have been described in which excessive TSH production from a pituitary tumour has caused hyperthyroidism (Hamilton et a]., 1970; Faglia et al., 1972; O’Donnell et al., 1973). In 1972 Emerson & Utiger described a seventh case in which hyperthyroidism was caused by excessive TSH production but no pituitary tumour was demonstrated, thus implying a possible hypothalamic aetiology mediated by TRH.
ACKNOWLEDGMENTS
I am grateful to Professor 0. L. Wade for permission to report this patient. 1 thank Dr S. M. Dirmikis who performed the LATS and LATSP assays, D r F. Maloof who measured serum TSH and alpha and beta subunits of human TSH, and Dr H. Schleusner who verified elevated TSH concentrations. REFERENCES T.H. (1967) Occurrence in thyrotoxicosis of a gamma globulin which protects ADAMS, D.D. & KENNEDY, LATS from neutralisation by an extract of thyroid gland. Journal of CIinical Endocrinology and Metabolism, 21, 173-1 77. ADAMS, D.D., KENNEDY, T.H. & STEWART, R.D.H. (1974) Correlation between long-acting thyroid stimulator protector level and thyroid 13’1 uptake in thyrotoxicosis. British Medical Journal, ii, 199-201. D’ANGELO, S.A., PASCHKIS, K.E., GORDON,A.S. & CANTAROW, A. (1951) Thyroid-thyrotropic hormone balance in the blood of normal and endocrinopathic individuals. Journal of Clinical Endocrinology, 11, 1237-1253. EMERSON, C.H. & UTIGER,R.D. (1972) Hyperthyroidism and excessive thyrotropin secretion. New England Journal of Medicine, 281, 328-333. FAGLIA,G., FERRARI,C., NERI,V., BECK-PECCOZ, P., AMBROSI. B. & VALENTINI, F. (1972) High plasma thyrotrophin levels in two patients with pituitary tumour. Acta Endocrinologica, 69, 649-658. HAMILTON, C.R., ADAMS,L.C. & MALOOF,F. (1970) Hyperthyroidism due to thyrotropin-producing pituitary chromophobe adenoma. New England Journal of Medicine, 283, 1077-1080. HERSHMAN, J.M. & HIGGINS,H.P. (1971) Hydatidiform mole-a cause of clinical hyperthyroidism. New England Journal of Medicine, 284, 573-577. JACKSON, I.M.D. (1965) Hyperthyroidism in a patient with a pituitary chromophobe adenoma. Journal of Clinical Endocrinology and Metabolism, 25,491-494. JAILER,J.W. & HOLUB,D.A. (1960) Remission of Graves’ disease following radiotherapy of a pituitary neoplasm. American Journal of Medicine, 28,497-500. KAPPELER, R. (1959) Hyperthyreose und Panhypopituitarismus im Verlauf eines chromophoben Adenoms der Hypophyse. Schweizerische Medizinische Wochenschrifr,89, 367-369. LAMBERG, B.-A., RIPATTI, J., GORDIN,A., JUUSTILA, H., SIVULA, A. & BJORKESTEN, G. (1969) Chromophobe pituitary adenoma with acromegaly and TSH-induced hyperthyroidism associated with parathyroid adenoma. Acta Endocrinologica, 60, 157-172. MAURER, W., WADER,A. & GLOOR, F. (1966) Hypophysenadenom, Hyperparathyreoidismus, und Hyperthyreose. Schweizerische Medizinische Wochenschrift, 96, 536-542. MCKENZIE, J.M. (1958) Delayed thyroid response to serum from thyrotoxic patients. Endocrinology, 62, 865-868. NURNBERGER, J.I. & KOREY, S.R. (1953) Pituitary Chromphobe Adenomas. Springer, New York.
150
P. H. Baylis
NYHAN,W.L. & GREEN,M. (1964) Hyperthyroidism in a patient with a pituitary adenoma. Journal of Pediatrics, 65, 583-589. ODELL,W.D., WILBER, J.F. & UTIGER, R.D. (1967) Studies of thyrotropin physiology by means of radioimmunoassay. Recent Progress in Hormone Research, 23,47-85. O'DONNELL, J., HADDEN, D.R. & WEAVER, J.A. (1973) Thyrotoxicosis recurring after surgical removal of a thyrotrophin-secreting pituitary tumour. Proceedings of the Royal Society of Medicine, 66,441442. STEIBIGEL, N.H., OPPENHEIM, J.J., FISHMAN, L.M. & CARBONE, P.P. (1964) Metastatic embryonal carcinoma of the testis associated with elevated plasma TSH-like activity and hyperthyroidism. New England Journal of Medicine, 271, 345-349. WERNER,S.C. & STEWART, W.B. (1958) Hyperthyroidism in a patient with a pituitary chromophobe adenoma and a fragment of normal pituitary. Journal of Clinical Endocrinology and Metabolism, 18, 266-277.
CASE O F H Y P E R T H Y R O I D I S M D U E TO A CHROMOPHOBE A D E N O M A * P. H . B A Y L I S
Department of Medicine, Queen Elizabeth Hospital, Birmingham
(Acceptedfor publication 9 September 1975)
SUMMARY
A 23-year-old man with secondary hypogonadism was also found to be thyrotoxic. Results of thyroid function tests were in the hyperthyroid range but the serum TSH was inappropriately high. A pituitary tumour was demonstrated and following hypophysectomy he became biochemically hypothyroid. Evidence is presented and discussed that his hyperthyroidism was due to excessive TSH production by the pituitary tumour. Hyperthyroidism is usually associated with immeasurably low serum thyroid stimulating hormone (TSH) concentrations. However, seven cases have now been reported in which excessive TSH production by the pituitary gland has been demonstrated, in two cases by bioassay (Jailer & Holub, 1960; Lamberg et al., 1969) and in five by radioimmunoassay (Hamilton et al., 1970; Faglia et al., 1972; O’Donnell et al., 1973; Emerson & Utiger, 1972). A further patient is described below who had hyperthyroidism due to excessive TSH production by a chromophobe adenoma. CASE HISTORY A 23-year-old male agricultural student was admitted to the Queen Elizabeth Hospital, Birmingham, in January 1974 for investigation of weight loss, lack of energy and loss of body hair since October 1972. He subsequently developed episodes of irritability associated with mild heat intolerance. Physical examination revealed a pale, smooth-skinned young man, height 181 cm and weight 65 kg. He had sparse axillary, facial and pubic hair. His thyroid gland was slightly enlarged but there was no associated bruit. Exophthalmos and lid-lag were not demonstrated. The testes were small. His pulse rate was 100/min, and there was marked proximal muscle weakness. Initial investigations confirmed the clinical suspicion of hyperthyroidism (Table 1).
* Presented at The Royal Society of Medicine, Endocrine Section, on 27 November 1974. Correspondence: Dr P. H . Baylis, Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH.
145
P. H. Baylis Thyroid scan was normal and thyroid antibodies were not found in the serum. A surprising result, in the face of hyperthyroidism, was a measurable serum TSH concentration of 5 mu/l (normal range 0-5 mu/l). The TSH concentration in the same sample was kindly measured by Dr H. Schleusner in Berlin and Dr F. Maloof in Boston, U.S.A.,both of whom found elevated levels (Table 1). Dr Maloof also measured alpha and beta subunits of TSH, both of which were not raised. TABLE1. Results of endocrine studies on presentation in January 1974 Patient Protein bound iodine (PBI) (pgldl) Serum thyroxine (T4) (pg/dl) Serum triiodothyronine (T3) fngfdl) T3 uptake test (%) Serum cholesterol (mg/dl) Basal TSH Dr Butt, Birmingham (mu/]) Dr Schleusner, Berlin (mu/l) Dr Maloof, Boston (pu/ml) TSH subunits: a-subunit (nglml) B-subunit (ng/ml) 13'1 uptake at 24 h (%) After T3 suppression (%) Thyroid antibodies Long acting thyroid stimulator (LATS) activity Long acting thyroid stimulator protector (LATSP) activity Urinary 17 oxosteroids (pmo1/24 h) Urinary 17 oxogenic steroids (pmo1/24 h) Serum testosterone (nmol/l) Serum total androgens (nmol/l) Plasma cortisol at 09.00 hours (nmol/l) Urinary free cortisol (nmo1/24 h) Basal prolactin (nglml) Basal growth hormone (mu/l) (no response to hypoglycaemia) Basal luteinizing hormone (LH) (u/l) Basal follicle stimulating hormone (FSH) (u/l) (no response to LHRH)
8.0 11.2 273 91 147 5
Normal 3'5-8.0 43-1 1.0 122-240 90-1 17 136-280
0-5 0.8-6.0 0-3'5
16.2 4.5 1.1 0.5 91.4 33.0 Negative
20-45 20-45 Negative
Negative
Negative
Negative 30 58 0.6 2.0 121 180 73 1
Negative 7-70 10-80 10-40 15-48 140-700 30-420 40 0-25
4 2
-
2-8 1-7
The serum total androgens were low (2-0 nmol/l), but adrenal function was satisfactory (urinary free cortisol 180 nmo1/24 h). Skull X-ray showed an enlarged pituitary fossa with erosion of the internal walls and a double contour to the floor. An air encephalogram showed no suprasellar extension. Basal serum TSH concentration was 5 mu/l and failed to rise after 200 pg of intravenous thyrotrophin releasing hormone. Serum prolactin was elevated and failed to increase further after TRH. Results of other relevant pituitary function tests are shown in Table 1. Perimetry of the visual fields was normal.
Hyperthyroidism due to a chromophobe adenoma
147
He was started on Carbimazole in February and within 2 months his thyrotoxicosis had improved clinically and biochemically (Fig. 1). On 1 May 1974 a transphenoidal hypophysectomy was performed by Mr G . A. Dalton. A large cystic tumour was removed, the histology of which revealed a chromophobe adenoma. He made an uneventful post-operative recovery and cortisone acetate replacement was started. He was thereafter seqn regularly in the Outpatients Department, where return of his secondary sexual features was noted. I
Hypophysectomy
- 5 mg 3 x 1 2 4 h I
Z"P
"-
.-
1 I2O 00
f
sol
-
1
-I
1
I
I
I
I
'
I
I
I
I
'
Months
FIG.1. Serial estimations of thyroxine, triiodothyronine, T3 uptake test and thyroid stimulating hormone from January 1974.
At the end of August 1974 he was readmitted for further assessment. His improved gonadal function was confirmed biochemically (total androgens 24 nmol/l). The thyroid function tests were mildly hypothyroid (serum T4 4.2 pg/dl, serum T3 70 ng/dl, T3 uptake test 107%) while the TSH level which had been almost undetectable immediately after surgery had returned to 5 mu/l and rose to 8 mu/l at 30 and 60 min after 200 p g TRH. The radioactive iodine uptake test returned to normal (30.6% at 24 h). There was a slight response of serum LH and FSH to LHRH, but no response of cortisol or growth hormone to insulin-induced hypoglycaemia. Basal serum prolactin was now in the normal range, and rose to 60 ng/ml after 200 pg TRH.
148
P.H. Baylis DISCUSSION
This young man presented with symptoms of hypogonadism shown to be due to a chromophobe adenoma of the pituitary gland. Clinically, hyperthyroidism was postulated to account for his marked weight loss, sweating, anxiety and tachycardia. A free thyroxine index based on serum PBI or serum T4 concentration combined with a T3 uptake test was definitely in the hyperthyroid range; serum T3 concentration was high and thyroidal uptake of l 3 'I was markedly elevated. These features seemed to confirm the presence of hyperthyroidism, which was further supported by his clinical and laboratory response to carbimazole. Two features militated against this diagnosis : measurable serum TSH concentration above our normal radioimmunoassay range, which was supported by D r Schleusner and Dr Maloof, and suppression of his thyroidal l 3'I uptake by triiodothyronine. Coincidental coexistence of hyperthyroidism and hypopituitarism would appear questionable from these findings, unless pituitary gland secretion of TSH was itself responsible for the hyperthyroidism. In this case, by anology with some benign adrenal tumours, incomplete suppression of thyroidal activity by triiodothyronine might be anticipated. Repeated TRH stimulation of the pituitary consistently showed no rise in the serum TSH concentration above the elevated basal levels; thus implying at least some suppression of the pituitary by circulating thyroid hormone. The failure of a rise in TSH following TRH is consistent with the diagnosis of hyperthyroidism. However, thyroidal l3 'I uptake was suppressed by triiodothyronine which is most unusual in hyperthyroidism and this probably indicates that the excessive TSH production was not autonomous. His skull X-ray suggested a pituitary tumour which was the most likely site of inappropriate TSH production. The pituitary origin of his hyperthyroidism was supported further by his clinical response to hypophysectomy, after which he became mildly hypothyroid with the serum TSH becoming undetectable. This later rose to its former level as he became euthyroid. Furthermore, following hypophysectomy his previously elevated serum prolactin levels returned to normal and showed a normal response to intravenous TRH, which may, in part, explain the return of hair growth and sexual activity. In this patient other possible causes of hyperthyroidism seemed unlikely. At no stage were there any clinical features of Graves' disease and neither LATS nor LATS protector activities were demonstrated (Adams & Kennedy, 1967; Adams et al., 1974). Non-suppression of thyroidal uptake of 13'1 by triiodothyronine is almost a sine qua non of Graves' disease or hyperthyroidism due to a toxic adenoma or multinodular goitre. This patient's thyroidal uptake suppressed dramatically indicating that the excessive thyroxine production was not autonomous. Hyperthyroidism associated with elevated serum TSH levels has been recorded in patients suffering from malignant disease including testicular carcinoma, hydatidiform mole and chorion-carcinoma, but no such disease was demonstrated in this patient (Steibigel et al., 1964; Hershman & Higgins, 1971). It was therefore concluded that this patient's hyperthyroidism was due to excessive TSH production by a chromophobe adenoma of the pituitary gland. Until 1960 there appear to have been eight cases reported of hyperthyroidism associated with chromophobe adenoma (Nurnberger & Korey, 1953; Werner & Stewart, 1958; Kappeler, 1959; Nyhan & Green, 1964; Jackson, 1965; Maurer et al., 1966). It had been presumed that these tumours had secreted excess TSH. In 1960, Jailer & Holub reported the
Hyperthyroidism due to a chromophobe adenoma
149
first case of hyperthyroidism and pituitary tumour in which the serum TSH was elevated, as measured by the bioassay technique of D’Angelo et al. (1951). In 1969 Lamberg et al., using a different bioassay (McKenzie, 1958), reported a patient with a chromophobe adenoma, acromegaly, hyperthyroidism and hyperparathyroidism. Since then radioimmunoassay of TSH (Ode11 et al., 1967) has been established and four further cases have been described in which excessive TSH production from a pituitary tumour has caused hyperthyroidism (Hamilton et a]., 1970; Faglia et al., 1972; O’Donnell et al., 1973). In 1972 Emerson & Utiger described a seventh case in which hyperthyroidism was caused by excessive TSH production but no pituitary tumour was demonstrated, thus implying a possible hypothalamic aetiology mediated by TRH.
ACKNOWLEDGMENTS
I am grateful to Professor 0. L. Wade for permission to report this patient. 1 thank Dr S. M. Dirmikis who performed the LATS and LATSP assays, D r F. Maloof who measured serum TSH and alpha and beta subunits of human TSH, and Dr H. Schleusner who verified elevated TSH concentrations. REFERENCES T.H. (1967) Occurrence in thyrotoxicosis of a gamma globulin which protects ADAMS, D.D. & KENNEDY, LATS from neutralisation by an extract of thyroid gland. Journal of CIinical Endocrinology and Metabolism, 21, 173-1 77. ADAMS, D.D., KENNEDY, T.H. & STEWART, R.D.H. (1974) Correlation between long-acting thyroid stimulator protector level and thyroid 13’1 uptake in thyrotoxicosis. British Medical Journal, ii, 199-201. D’ANGELO, S.A., PASCHKIS, K.E., GORDON,A.S. & CANTAROW, A. (1951) Thyroid-thyrotropic hormone balance in the blood of normal and endocrinopathic individuals. Journal of Clinical Endocrinology, 11, 1237-1253. EMERSON, C.H. & UTIGER,R.D. (1972) Hyperthyroidism and excessive thyrotropin secretion. New England Journal of Medicine, 281, 328-333. FAGLIA,G., FERRARI,C., NERI,V., BECK-PECCOZ, P., AMBROSI. B. & VALENTINI, F. (1972) High plasma thyrotrophin levels in two patients with pituitary tumour. Acta Endocrinologica, 69, 649-658. HAMILTON, C.R., ADAMS,L.C. & MALOOF,F. (1970) Hyperthyroidism due to thyrotropin-producing pituitary chromophobe adenoma. New England Journal of Medicine, 283, 1077-1080. HERSHMAN, J.M. & HIGGINS,H.P. (1971) Hydatidiform mole-a cause of clinical hyperthyroidism. New England Journal of Medicine, 284, 573-577. JACKSON, I.M.D. (1965) Hyperthyroidism in a patient with a pituitary chromophobe adenoma. Journal of Clinical Endocrinology and Metabolism, 25,491-494. JAILER,J.W. & HOLUB,D.A. (1960) Remission of Graves’ disease following radiotherapy of a pituitary neoplasm. American Journal of Medicine, 28,497-500. KAPPELER, R. (1959) Hyperthyreose und Panhypopituitarismus im Verlauf eines chromophoben Adenoms der Hypophyse. Schweizerische Medizinische Wochenschrifr,89, 367-369. LAMBERG, B.-A., RIPATTI, J., GORDIN,A., JUUSTILA, H., SIVULA, A. & BJORKESTEN, G. (1969) Chromophobe pituitary adenoma with acromegaly and TSH-induced hyperthyroidism associated with parathyroid adenoma. Acta Endocrinologica, 60, 157-172. MAURER, W., WADER,A. & GLOOR, F. (1966) Hypophysenadenom, Hyperparathyreoidismus, und Hyperthyreose. Schweizerische Medizinische Wochenschrift, 96, 536-542. MCKENZIE, J.M. (1958) Delayed thyroid response to serum from thyrotoxic patients. Endocrinology, 62, 865-868. NURNBERGER, J.I. & KOREY, S.R. (1953) Pituitary Chromphobe Adenomas. Springer, New York.
150
P. H. Baylis
NYHAN,W.L. & GREEN,M. (1964) Hyperthyroidism in a patient with a pituitary adenoma. Journal of Pediatrics, 65, 583-589. ODELL,W.D., WILBER, J.F. & UTIGER, R.D. (1967) Studies of thyrotropin physiology by means of radioimmunoassay. Recent Progress in Hormone Research, 23,47-85. O'DONNELL, J., HADDEN, D.R. & WEAVER, J.A. (1973) Thyrotoxicosis recurring after surgical removal of a thyrotrophin-secreting pituitary tumour. Proceedings of the Royal Society of Medicine, 66,441442. STEIBIGEL, N.H., OPPENHEIM, J.J., FISHMAN, L.M. & CARBONE, P.P. (1964) Metastatic embryonal carcinoma of the testis associated with elevated plasma TSH-like activity and hyperthyroidism. New England Journal of Medicine, 271, 345-349. WERNER,S.C. & STEWART, W.B. (1958) Hyperthyroidism in a patient with a pituitary chromophobe adenoma and a fragment of normal pituitary. Journal of Clinical Endocrinology and Metabolism, 18, 266-277.
