Multiglandular disease in seemingly sporadic primary hyperparathyroidism revisited: where are we in the early 1990s? A plea against unilateral parathyroid exploration.

BACKGROUND: Most of the available data on multiglandular disease (MGD) originate from long-term series. The spectrum of the disease has changed now because of earlier diagnosis. We decided to assess the current frequency of MGD in seemingly sporadic primary hyperparathyroidism. METHODS: MGD was defined as the finding that more than one grossly enlarged gland weighed more than 50 mg and the rim of normal parathyroid tissue was diagnostic of adenoma. Nine hundred eight consecutive neck explorations for hyperparathyroidism were performed, 624 before 1989 and 284 between 1989 and 1991, and studied retrospectively. Since 1989, oil Red O staining has been done to assess hyperfunction. RESULTS: When multiple endocrine neoplasia and non-multiple endocrine neoplasia familial cases of hyperparathyroidism are excluded, the frequency of MGD in seemingly sporadic primary hyperparathyroidism, 17.7% before 1989, is still 14% since then, including a 3% frequency of true multiple adenomas. With more restrictive criteria, which exclude the second enlarged gland if it weighed less than 100 mg, if it had no rim, and if oil Red O staining was negative, the frequency of MGD in sporadic hyperparathyroidism has remained 11% since 1989. Unilateral exploration had missed 78% of second enlarged glands, and preoperative imaging studies, when performed, showed more than one gland in only two of 22 cases. CONCLUSIONS: Routine bilateral neck exploration is recommended in primary hyperparathyroidism because of a current frequency of MGD of at least 11%.

Usefulness and limits of quick intraoperative measurements of intact (1-84) parathyroid hormone in the surgical management of hyperparathyroidism: sequential measurements in patients with multiglandular disease.

This study was designed to assess whether reliability of quick intraoperative assay of intact (1-84) immunoreactive parathyroid hormone (iPTH) could allow us to quit after removing one (or several) enlarged parathyroid gland(s) and obtaining a normal iPTH level. Intact iPTH was assayed during surgery before removal of enlarged parathyroid gland(s) and 5, 10, and 20 minutes afterward. Forty-seven patients entered the study: 40 with primary hyperparathyroidism (32 with uniglandular disease and eight with multiglandular disease) and seven with secondary hyperparathyroidism; all underwent bilateral neck exploration. Among 32 patients with uniglandular disease, five had normal basal intraoperative levels, 25 demonstrated a clear-cut drop from supranormal to normal levels, and two had elevated levels. Among the eight patients with multiglandular disease, two had undetectable levels and two had normal levels after removal of the first enlarged gland. The seven patients with secondary hyperparathyroidism demonstrated a decline in PTH levels, suggesting hormone clearance similar to that of patients with primary hyperparathyroidism. In conclusion, quick intraoperative assay with intact (1-84) iPTH (1) is not hampered by renal insufficiency, (2) may overlook a second enlarged gland after removal of a first adenoma and obtaining normal iPTH levels, and (3) should not be used as a substitute for bilateral neck exploration.

[Hyperparathyroidism and intrathyroid parathyroid gland. 43 cases]. / Hyperparathyroïdie et parathyroïde intrathyroïdienne. 43 observations.

The rate of occurrence of intrathyroidal parathyroid glands in patients treated surgically for hyperparathyroidism (HPT) varies across studies. Among 1200 consecutive patients who underwent surgery for HPT at the Lille Hospital, France, between December 1965 and July 1992, 43 (3.6%) had 47 histologically-proven intrathyroidal parathyroid glands, including 44 lower and three upper parathyroid glands. Fifteen patients had a thyroid gland abnormality. Of the 14 patients who had a preoperative ultrasound study, eight exhibited an abnormal image. Thirty-four of the 47 intrathyroidal parathyroid glands were visible at the surface of the thyroid gland, five were felt on palpation, and eight were discovered upon examination of a lobectomy specimen. A normal or abnormal parathyroid gland can be completely concealed within the thyroid gland, even in the absence of concomitant thyroid gland disease. In most cases, the ectopia affects one or both lower parathyroid glands, although in some instances the two glands on the same side are intrathyroidal. There is no fail-proof means for detecting intrathyroidal parathyroid glands preoperatively. An apparently missing fourth parathyroid gland or a fifth gland should be looked for in the thyroid gland when the cause of HPT is not found during a first cervicotomy procedure. Pre- or intra-operative ultrasonography may be the most informative imaging method for detecting intrathyroidal parathyroid glands and should be performed routinely when a repeat procedure for persistent HPT is being considered.

[Reoperation for persistent or recurrent primary hyperparathyroidism. Seventy-seven cases among 1888 operated patients]. / Réinterventions pour hyperparathyroïdisme primaire persistant ou récidivant. Soixante-dix-sept cas sur 1888 opérés.

AIMS: To analyse the results of re-operations for persistent (p) or recurrent (r) primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: From 1965 throughout 2001, 1888 patients were operated on for PHPT. The cure rate after initial surgery was 97.6%. Seventy-seven (4.1%) were reoperated for p PHPT (n = 54) or r PHPT (n = 23). Thirty-two out of 77 (41%) had been primarily operated elsewhere. In 15 cases (20%) PHPT was genetically determined. The re-operation was undertaken on average 40.7 months after initial surgery (1 day-190 months). RESULTS: Two out of 77 were cases of familial hypocalciuric hypercalcaemia. Among the 75 patients reoperated for true PHPT, 23 (31%) had uniglandular disease (UGD) and 52 (69%) had multiglandular disease (MGD). There were two cases of recurrent parathyroid carcinoma. Overall 97 pathological glands were resected, 37% being orthotopic and 63% heterotopic. The re-operation was performed by a cervical approach in 80%, by a mediastinal approach in 15%, whereas 5% involved excision of antebrachial implants. In 96% of cases the parathyroid glands were in the cervical position. Among the preoperative localisations studies the sensitivity of scintigraphy utilising 2-methoxyisobutyl-isonitril (MIBI) was 61%. Utilising both MIBI and cervical ultrasound the sensitivity was 64%. Sixty-eight out of 75 (91%) were cured of their hypercalcaemia, but at the cost of permanent hypoparathyroidism in 9% of cases. No sporadic adenoma appears to have been missed. The seven failures after re-operation (9%) involved five cases of MGD, of which four were sporadic, two cases of carcinoma and one case of parathyreomatosis. 39 patients (51%) had more than four parathyroid glands and in 22/39 cases at least one supernumerary gland was pathological. CONCLUSION: The re-operations for PHPT were essentially due to MGD that was either sporadic or genetically determined. Often the offending supernumerary gland was not detected by imaging studies. Avoiding failures entails an initial bilateral cervicotomy with thymic exploration after MIBI scintigraphy to exclude a mediastinal focus.

[Multi-glandular lesions in primary hyperparathyroidism. Late outcome of 86 consecutive patients treated with conservative surgery]. / Lésions multi-glandulaires de l'hyperparathyroïdie primaire. Devenir tardif de 86 patients consécutifs traités par chirurgie conservatrice.

Multiple gland enlargement (M.G.E.) in primary hyperparathyroidism (H.P.T.) is the presence of 2 or more enlarged glands weighing more than 50 mg. Conservative surgery (C.S.) consists of resecting the grossly enlarged glands without biopsying the normal glands. Some authors have suggested that C.S. might overlook minute hyperplasia, hence leading to late recurrences of H.P.T., or conversely result in the unnecessary resection of grossly enlarged, but not hyperfunctioning glands. 379 patients have been operated upon for H.P.T. 86 (22.7%) had M.G.E. including 13 (15.2%) M.E.N. cases, 8 (9.3%) familial cases and 65 (75.6%) seemingly sporadic cases (S.S.C.). 2, 3 or 4 glands (or more) were involved in 39.5%, 35% and 25.5% of cases respectively. 1 patient died post-operatively and 3--all S.S.C. with hyperplasia--had to be reoperated upon within 1 year for persistent hypercalcemia. Pathological diagnosis was: double adenomas in 5.8%, hyperplasia in 36%, adenoma associated with hyperplasia in 46.5% and a normal second gland, on light microscopy findings in 11.7%. None of 13 deaths occurring during follow-up was related to H.P.T. 78 patients (90.7%) are available for follow-up (av. 85.3 months). 85.9% are normocalcemic (2.2 less than Ca less than 2.6 mmol/l), 5.1% hypocalcemic and 9% hypercalcemic. 61 had late i. P.T.H. assay; i. P.T.H. was appropriate to serum calcium in 78.7% and appropriate to normal serum calcium levels in 90.6% of 53 normocalcemic cases.

Reoperation for persistent or recurrent primary hyperparathyroidism.

AIM: To analyse the causes and outcome of reoperations for persistent or recurrent primary hyperparathyroidism (HPT). MATERIALS AND METHODS: We reviewed the medical records of 38 patients who underwent reoperation between December 1965 and April 1997 for persistent or recurrent primary HPT. During this period of time, 1448 patients underwent operation for primary HPT, 294 for renal HPT and 58 for questionable disease, i. e. a total of 1800. In the 1448 cases of HPT, 22 patients were reoperated after a first cervicotomy in the institution, i. e. a first reoperation rate of 1.5%. Sixteen patients were referred after unsuccessful parathyroid surgery. Six patients were reoperated on twice and one patient seven times for a graft-dependent recurrence. RESULTS: Reasons for failed parathyroid operations included tumour tissue in ectopic location (75%) or tumour tissue that had not been seen in normal position (19%), parathyreomatosis (2%), parathyroid cancer (2%) and graft-dependent hypercalcaemia (2%). Of the ectopic glands, 45 % were intrathymic, 12.5% intrathyroidal, 7.5% retro-oesophageal, 7.5% in the carotid sheath, 5% interthyrotracheal, 5% in the mediastinum (extrathymic), 5% in the aorto-pulmonary window, 2.5% undescended, 2.5% overdescended and 2.5% intertracheooesophageal. Of the patients, 38% had uniglandular lesions, 60% multiglandular lesions, and 2% parathyroid cancer. The histologically confirmed cause of HPT was adenoma in 50% of cases, hyperplasia in 38% and "normal" but overweight glands in 9.5%. Of the 38 patients studied, 15 presented one or more supernumerary glands (fifth to eighth gland). Reoperation was performed through a cervical incision in 82% of cases and using a mediastinal approach in 18% (8 median sternotomies, 1 thoracoscopy). The success rate of the reoperations was 92%. A total of 8% of patients suffered permanent unilateral vocal cord paralysis; 5% are definitely hypocalcaemic. The sensitivities of preoperative localization studies ranged from 69% for sestamibi scan and 63% for selective venous catheterization to 16% for computed tomography. CONCLUSION: Repeated parathyroidectomy can be avoided in more than 98% of patients if an experienced surgeon performs bilateral cervical exploration during the initial parathyroid operation. For patients with persistent or recurrent primary HPT, preoperative localization studies and a focused surgical approach can result in a 92% success rate with a minimal complication rate.

Late outcome of 304 consecutive patients with multiple gland enlargement in primary hyperparathyroidism treated by conservative surgery.

The aim of this study was to assess the late outcome of patients with primary hyperparathyroidism and multiple gland enlargement (MGE) treated by conservative surgery. MGE in primary hyperparathyroidism is the presence of two or more enlarged glands weighing more than 50 mg. Conservative surgery consists in resecting the grossly enlarged glands without biopsying the normal glands. Some authors have suggested that this approach overlooks minute hyperplasia, leading to late recurrences of hyperparathyroidism; conversely, it may result in the unnecessary resection of grossly enlarged, but not hyperfunctioning, glands. Altogether 1231 patients were operated on for primary hyperparathyroidism between 1966 and 1995. Of these patients, 304 (24.9%) had MGE, including 42 cases of multiple endocrine neoplasia (MEN), 12 familial cases, and 250 seemingly sporadic cases. Two, three, or four glands (or more) were involved in 61.8%, 21.4%, and 16.4% of cases, respectively. During the early postoperative period one patient died and ten were reoperated for persistent hypercalcemia. The pathologic diagnoses were double adenomas (13.5%), hyperplasia (35.8%), association of the two (39.8%), and a normal second gland (10.8%) on light microscopy findings. None of the 30 deaths that occurred during follow-up was related to hyperparathyroidism. Altogether 190 patients (79%) were available for follow-up (average 89.3 months): 90% were normocalcemic, 4.7% hypocalcemic, and 5.2% hypercalcemic. A late iPTH assay was done in 147. PTH was appropriate to the serum calcium level in 84.3% and appropriate to normal calcemia in 91.6% of 132 cases. Conservative surgery is thus an acceptable treatment for MGE in patients with hyperparathyroidism. Few late recurrences occur, for which there are no individual predictive criteria.

[Decision-making for lymph node excision in surgery of thyroid cancer. Extemporaneous examination of the external supraclavicular lymph nodes]. / Décision de curage ganglionnaire en chirurgie du cancer thyroïdien. Apport de l'examen extemporané des ganglions sus-claviculaires externes.

UNLABELLED: Modified neck dissection (MND) is not recommended for surgery of thyroid carcinoma (TC) in the absence of grossly involved nodes, except for medullary thyroid carcinoma, and clinical node recurrence in uncommon at follow-up (3% for us). But several authors report metastatic cancer in non-palpable nodes up to 70% on MND specimens. The fear of overlooking occult metastatic nodes prompted us to sample even normal appearing nodes and to rely on frozen sections (FS) to make a decision whether or not a MND should be done. PATIENTS AND METHODS: 130 among 300 consecutive patients operated for TC were submitted to supraclavicular node sampling with FS. All pathological varieties were covered. In 170 cases, sampling was not done purposely (lack of intraoperative diagnosis of carcinoma: 75) or for other reasons (absence of obvious nodes: 77; unavailable pathologist: 14; miscellaneous: 4). All specimens were reviewed by paraffin sections (PS). RESULTS: Among the 130 patients; 25 had gross metastatic node involvement, confirmed by FS+ and PS+; 1 had grossly equivocal nodes with FS- and PS+; 104 had grossly normal nodes. In 101 (97%) this was confirmed by FS- and PS-. In 3 (3%) FS was +, leading to MND, and PS confirmed metastatic involvement in 2. All 32 specimens of routine node sampling done in 1988 have been reviewed by serial cross sections, one each millimeter (331 sections). One only disclosed one occult metastatic invasion. CONCLUSION: No more than 3% of the grossly normal supraclavicular nodes are metastatic at the time of surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Urodynamics in patients with pheochromocytoma: a peri-operative study of 10 cases.

Alpha receptors have been demonstrated in the bladder neck, and urinary retention may be the presenting symptom in an occasional pheochromocytoma patient. This prompted us to define the urodynamic profile in pheochromocytoma patients. Ten patients were studied. Except for 2 patients, all tumors secreted norepinephrine either alone (n = 4) or mixed (n = 4). Urodynamic studies (uroflowmetry, cystometry, profilometry, response to alpha-adrenergic agents) were performed with Urodyn 5000 chain (DANTEC) connected to a water perfused Bohler's catheter. Profilometry was done according to the Brown and Wickham technique. Normal values were those of the International Continence Society. Alpha blocker test was done by intravenous injection of thymoxamine (0.5 mg/kg) and was considered as positive if urethral closure pressure (UCP) decrease was greater than 30% after 10 minutes. Ten patients had a pre-operative study, omitting alpha-blocker test in 1 patient; 5 patients consented a postoperative study. Pre-operatively we could demonstrate: 1) Increased UCP in 8 of 10 patients, regardless of the secretory pattern; 2) Response to alpha-adrenolytic agents in 7 of 9 patients; and postoperatively: 3) Good correlation between a positive alpha-blocker test and a decrease in urethral pressure in 3 of 5 patients. Urodynamics in pheochromocytoma patients show a typical alpha-adrenergic pattern and may explain bladder dysfunction as a presenting symptom.

Primary hyperparathyroidism due to solitary adenoma. A comparative multicentre study of early and long-term results of different surgical regimens.

Surgical regimens for treatment of solitary parathyroid adenoma were compared in a multicentre study in five departments of surgery in the United States and Europe. Three hundred and twenty-five patients fulfilled the inclusion criteria. Eight years after the operation 272 patients (84%) were available for follow-up investigation. Severe postoperative hypocalcaemia (less than 2.00 mmol) was significantly more common after bilateral than unilateral exploration (p less than 0.001), and in women (p less than 0.01). Neither age nor preoperative serum calcium concentration was related to the severity of postoperative hypocalcaemia. At follow-up, 96% of the patients who had had unilateral, and 89% of those who had had Bilateral exploration had remained normocalcaemic without further treatment. Of the patients who had had incisional biopsies of normal glands 8% had hypercalcaemia and 8% had hypocalcaemia. Of patients operated on without a biopsy being taken or who had had one whole normal gland removed 1% were hypercalcaemic and 4% were hypocalcaemic. Early and late hypocalcaemia are reduced by atraumatic handling of the normal parathyroid gland without increasing the risk of persistent or recurrent hypercalcaemia.