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The case reports on two patients with medullary thyroid carcinoma show that even postoperatively stimulated serum calcitonin (CT) concentrations near the detection limit (using a polyclonal antibody against synthetic CT) can demonstrate persistent disease. Stimulated CT concentrations can be lowered to nondetectable levels by a second and third operation if a meticulous technique is used for dissection of the lymph compartments. The patient can then be assumed to be cured. Diagnostic accuracy at very low CT concentrations can be improved by selective venous catheterization with blood sampling for CT after stimulation.

Mechanically dissociated cells from a surgically removed mediastinal C-cell carcinoma (MTC) were cultured over a period of 4 months. The cells of the monolayer culture consisted of clusters of small epithelial-like cells. Using semithin and ultrathin sections, two different types of cells could be characterized by shape of nucleus and by content and distribution of secretory granules. One type of cell showed a more irregularly shaped nucleus, the other contained a large oval nucleus, similar to the normal C-cell of the human thyroid. Calcitonin (CT) and carcinoembryonic antigen (CEA) were measured in supernatants in duplicate by radioimmunoassays. Radioimmuno-detectable CT levels in the supernatant of culture medium varied between 0.8 and 1.6 ng/ml and CEA levels between 5 and 27 ng/ml during a 2-month period. The present study proves that in monolayer-cultured cells of a MTC, metastases continue to produce radioimmuno-detectable CT and CEA. Whether the two different cell types in culture are relevant for carcinoma needs further investigation.

C-cell tumours are rare in children. They must be classified as hereditary types of the C-cell carcinomas. C-cell hyperplasias are considered as obligatory precanceroses of this malignoma. The article reports on two cases of C-cell hyperplasia discovered within the framework of a family screening study. Attention is drawn to the importance of screening for diagnosis of early tumour stages resulting in improved prognosis.

An increased activity of vasoconstrictor mechanisms may play an important role in circulatory adjustments to heart failure. Thus, hemodynamic data and the plasma hormones epinephrine (E), norepinephrine (NE) and arginin vasopressin (AVP) as well as the plasma renin activity (PRA) were assessed in 50 patients undergoing coronary angiography and right heart catheterization. Patients were classified into three groups according to severity of left ventricular (LV) dysfunction as assessed by ejection fraction (LVEF): those with normal left ventricular function (group 1 (n = 12): LVEF greater than or equal to 55%, mean 70 +/- 3%) and those with moderate (group 2 (n = 16): LVEF 54-35%, mean 43 +/- 2%) or severe LV dysfunction (group 3 (n = 22): LVEF less than 35%, mean 22 +/- 1%). At rest plasma NE concentrations in patients with heart failure (group 2: 187 +/- 17 pg/ml; group 3: 299 +/- 27 pg/ml) did not differ significantly from control values (199 +/- 26 pg/ml). During exercise, NE concentrations increased in all patients (p less than 0.001). This increase in plasma NE was more pronounced in group 3 (753 +/- 71 pg/ml) than in group 1 (262 +/- 37) and group 2 (388 +/- 64). A significant inverse correlation was found between plasma NE and stroke index at rest (r = -0.592, p less than 0.001) as well as during exercise (r = -0.659, p less than 0.001). PRA was elevated at rest and during exercise in patients of group 3 but not of group 2 as compared with control patients (p less than 0.05). Plasma E and AVP were similar in all groups. Patients of group 3 were subdivided according to exercise capacity into patients who tolerated a maximum work load of 50 watts or more (group 3A) and those who did not tolerate a work load exceeding 25 watts (group 3B). At rest and during exercise, patients of group 3A had a higher stroke index than patients of group 3B. In contrast, there was no significant difference in LVEF between group 3A and 3B (22 +/- 2 vs 20 +/- 1%). During exercise patients with low exercise capacity (group 3B) had higher NE levels than patients with less impaired exercise capacity (group 3A) (948 +/- 86 vs 590 +/- 65 pg/ml, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clodronate (dichlormethylene diphosphonate) was administered to 21 patients with hypercalcemia due to malignant tumor. The drug was initially given intravenously, then orally. In 20 patients the serum calcium level had been reduced to the normal range within one week of the start of treatment (from 3.3 +/- 0.5 mmol/l to 2.4 +/- 0.3 mmol/l). With oral administration there was a renewed rise in calcium levels in some patients, which had to be treated with higher oral doses or intravenous administration. Parallel with the reduction in calcium levels there was an improvement in the originally impaired renal function. The serum level of intact parathormone(1-84) and 1.25-dihydroxy-vitamin-D3 (calcitriol) rose significantly from usually lowered initial levels. There was a non-linear inverse correlation between parathormone and calcium. No side effects were noted, even after long-term administration.

Following introductory remarks on the connected literature, a report is given on personal experience in the diagnosis and treatment of primary hyperparathyroidism (p.hpt) in a 14 years old girl. Clinical symptomatology and predominant form of organic manifestation as well as special biochemical diagnostic procedures of p.hpt in childhood are discussed. The necessity of longterm postoperative controls until complete regeneration of skeletal lesions and of adequate therapeutic Ca++-substitution is stressed.

Serum levels of the peptide hormones, LH, FSH, TSH, prolactin, beta-HCG and PTH are observed to significantly modulate in patients with urogenital tumors, beta-HCG appears elevated in patients with chorioncarcinoma, teratoma and embryonal carcinoma and is shown to increase serum prolactin. TSH and prolactin are measured in pathological range in patients with renal carcinomas. Following nephrectomy serum TSH persists in high levels only in patients with advanced diseases, while PTH is more frequently suppressed in these patients. Serum LH and prolactin show a more distinct change of values in infiltrating bladder cancer, when compared to that of noninvasive bladder carcinomas. Prostate benign hyperplasia and cancer demonstrate similar ranges for peptide hormones, that will be changed by estrogen treatment in its LH, TSH and prolactin pattern. Serum levels of peptide hormones are affected by a complex system of ectopic hormone production, synthesis of peptide analogues, metabolic changes due to age and treatment.

C-cell carcinoma (medullary thyroid carcinoma) is associated with increased serum calcitonin levels. In addition, increased serum levels of other tumour markers are also found: carcinoembryonic antigen (CEA), adrenocorticotrophic hormone (ACTH) and tissue polypeptide antigen (TPA). The relevance of these tumour markers as compared to calcitonin was evaluated in 46 patients with C-cell carcinoma. With decreasing frequency pathologically increased levels were found: calcitonin 93%, CEA 73%, TPA 17% and ACTH 8%. There was a positive correlation between calcitonin and CEA values. Calcitonin and CEA levels correlated with the clinical tumour stage. In selective venous catheterisation estimation of calcitonin is superior to estimation of CEA. Assessment of CEA supplements calcitonin measurements in follow-up controls and evaluation of success of treatment. As regards specificity and sensitivity calcitonin is superior to all other tested tumour markers in C-cell carcinoma.

Nine male healthy volunteers were examined during a control period, during an oral glycine load (45 g/day, 600 mmol) and oral methionine (6 g/day, 40 mmol). Glycine caused a significant increase of urinary oxalate above baseline (from 644 to 797 mumol/day) without change in calciuria (4.74 vs 4.84 mmol/day). In contrast methionine caused no change of oxaluria, but a significant increase in calciuria (from 4.74 to 6.9 mmol/day). Alterations of lithogenic ions in urine after protein ingestion are mediated by different amino acids. The particular lithogenic risk of animal protein may be related to its high methionine/cystine and glycine content.

The effect of beta-sitosterol on the lipid and lipoprotein level was evaluated in a randomised double-blind cross-over trial in 24 patients with primary familial type II hyperlipoproteinaemia over a period of 16 weeks. All patients completed the trial, however 10 of them had to be excluded from the evaluation due to fluctuations of their body weight or unreliable drug intake. Sitosterol lowered the total cholesterol level by 12.5% (P less than 0.01) from 9.96 mmol/l (3.69 g/l) to 8.37 mmol/l (3.23 g/l). The LDL-cholesterol level was lowered by 19.5% (P less than 0.05). The sitosterol concentration in plasma was consistently lower than 0.3% of total cholesterol. No side effects or tachyphylaxis was observed in the course of the trial. A return to normal of an increased serum cholesterol level by a combination of a lipid lowering diet and sitosterol monotherapy was only achieved in one patient.

In 10 patients with early renal failure (glomerular filtration rate between 30 and 80 ml/min/1.73 m2) without nephrotic syndrome and in 13 controls the calciuric response to increasing oral doses of calcitriol [1,25-(OH)2D3] (0.25; 0.5; 1.0; 1.5 micrograms/day) was evaluated. Patients had initially normal plasma calcitriol levels, normocalcemia and hypocalciuria. With calcitriol doses up to 1 microgram/day, the increment of UVCa was less in patients. Only at 1.5 micrograms/day the calciuria of patients reached the baseline calciuria of controls. The data document that 1.0 microgram calcitriol per day is required to normalize UVCa in patients with early renal failure and normal calcitriol levels. Blunted calciuric response to low doses of calcitriol is compatible with an altered dose-response relationship.

We performed simultaneous measurements of CA 12-5, CEA and Ca 19-9 in the preoperative sera of 87 patients with gastric cancer, 177 patients with colo-rectal cancer and 55 patients with benign diseases. 5.6% of the control patients, 13.8% of the gastric cancer patients and 9.6% of the colo-rectal cancer patients showed Ca 12-5 values of 27.0 U/ml and more. In contrast, the sensitivity of the tumor markers CEA (greater than or equal to 5.0 ng/ml in 17.1% of the gastric cancer and 36.2% of the colo-rectal cancer patients examined) and Ca 19-9 (greater than or equal to 25.0 U/ml in 16.1% of the gastric cancer and 19.8% of the colo-rectal cancer patients) was distinctly higher. The simultaneous determination of three markers on the one hand increased the rate of 'marker-positive' patients (up to 34.5% in gastric cancer and 45.2% in colo-rectal cancer) but on the other hand diminished the specificity (from 96.4% to 89.1%) of the examination.

We investigated the immunological heterogeneity of plasma Tg in thyroid cancer patients using monoclonal antibodies in an immunoradiometric assay and a conventional RIA system with a polyclonal rabbit antibody. The results were compared with measurements of plasma Tg in patients with nonmalignant disease. We can demonstrate an increased immunological heterogeneity in tumor patients compared with patients with non-malignant thyroid diseases. In one case the Tg value measured by a monoclonal test system exceeded the value obtained by a polyclonal RIA system in the same sample by a factor of 25. It has to be further investigated whether this increase in heterogeneity is of diagnostic value in the follow-up of thyroid cancer patients.

The effects of pulsatile and nonpulsatile flow pattern on pancreas and liver blood flow were studied in nine dogs on cardiopulmonary bypass (CPB). Furthermore, plasma levels of glucose, insulin, glucagon, growth hormone, and cholinesterase were compared in 20 patients subjected to open heart surgery with either pulsatile or nonpulsatile perfusion. Impairment of liver and pancreas function was significantly greater at the end of CPB and 48 h afterwards with nonpulsatile flow as compared with the pulsatile flow pattern. A decrease of intestinal blood flow that was demonstrated in dogs subjected to nonpulsatile perfusion could at least in part be responsible for the difference in postoperative organ function observed in patients after CPB.

In a study of the immunoglobulin concentrations in an urban population and in patients with hyperlipoproteinemia we observed significant positive correlations between serum triglycerides and IgA independent of sex, age and body weight. In men serum triglycerides also correlated with IgG and IgM, and serum cholesterol with IgA. The prevalence of hyper- and hypoimmunoglobulinemia was significantly higher in hyperlipidemic than in normolipemic subjects. We propose that the occurrence of hyperlipoproteinemia with hypoimmunoglobulinemia may be caused by different pathobiological mechanisms than the occurrence with hyperimmunoglobulinemia.

High dose levels of calcium chloride significantly decrease serum level of parathyroid hormone (PTH) in both patients with history of idiopathic stone formation and healthy controls. Suppressibility of parathyroid glands is obtained by injection of 10 ml 10% calcium chloride without any restriction in calcium diet. Serum levels of calcium measured 14 mg/dl 10 min. after high dose calcium chloride injection and distinctly affect cAMP in urine in patients when compared to healthy controls. The elimination of electrolytes and uric acid is elevated 40 min. after calcium application in both patients and controls and returns to normal values 120 min. later. No stone formation has been observed in an eighteen mouth follow up of all subjects studied.

Longterm treatment for 5 years of young patients with familial hypercholesterolemia was accompanied by monitoring of plasma levels of calcium, iron, sodium, parathyroid hormone and water- and fat soluble vitamins, since interference of the ion exchange resin with absorption of numerous substances as well as abnormal plasma levels of some of the above had been described in several studies. Treatment was effective in the group with good compliance (lowering of plasma cholesterol at the end of 5 years by 19% and, compared to the control group, by 23%). Adverse drug effects with respect to the above parameters were not found. Plasma levels of carotinoides and vitamin E were elevated in the patients according to elevated concentrations of lipoproteins which are carriers of these vitamins.

We compared the utility of measurements of serum intact human PTH-(1-84) and midregion human PTH-(44-68) in patients with disorders of extracellular calcium metabolism. Serum midregion PTH was determined by RIA, and serum intact PTH was measured by a sensitive and specific immunoradiometric two-site assay. The serum intact PTH concentrations in 70 patients with primary hyperparathyroidism were above the normal range in 69, and thus widely separated from the levels in 40 patients with hypercalcemia of malignancy, in whom serum intact PTH values were usually below normal. In contrast, both groups had overlapping serum midregion PTH values. In patients after renal transplantation and those with chronic renal failure, serum intact PTH levels were in the normal range twice as often as were serum midregion PTH values. The intact PTH assay was also superior in detecting venous gradients of the hormone and changes in PTH secretion caused by altered serum calcium concentrations, and serum intact PTH was remarkably low in hepatic venous effluent. We conclude that this new assay for serum intact PTH is superior to the midregion RIA in investigating parathyroid function in several different clinical conditions.

We studied six different antisera to bovine or porcine parathyrin (parathyroid hormone, PTH), produced in rabbit, guinea pigs, sheep or goat, two of which are commercially available. The antisera were characterized with regard to species specificity, affinity and their ability to identify patients with primary hyperparathyroidism. In this heterologous radioimmunoassay system in which [125I]parathyrin is used as a tracer, some cross-reactivity of the antisera to the hormone or hormone fragments present in human serum was demonstrated. However, there is some overlap of serum immunoreactive parathyrin in patients with or without primary hyperparathyroidism. The results of this and other studies illustrate the necessity for a homologous radioimmunoassay for human parathyrin.

The effect of acute and chronic ethanol administration on DNA synthesis in the gastrointestinal tract of the rat was investigated. Acute intragastric ethanol administration (3 g/kg; 50%) decreased significantly in vivo DNA synthesis when measured 1 hour after alcohol application in the stomach and in the upper small intestine, whereas acute intravenous ethanol administration had no significant effect. In contrast, chronic ethanol ingestion resulted in a significant increase of in vivo and in vitro DNA synthesis in the upper gastrointestinal tract. In addition, even a more enhanced stimulation of DNA synthesis after chronic ethanol consumption was found in isolated intestinal cells. These results indicate an inhibition of gastrointestinal cell regeneration directly after the oral application of ethanol. The enhanced cellular regenerativity observed after chronic ethanol consumption may be secondary to the ethanol induced damage of the gastrointestinal tract.

A sensitive radioimmunoassay system for 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] with an improved extraction procedure has been developed. Following one-step extraction and prepurification of 1,25(OH)2D3 by 'Extrelut-1' minicolumns final purification was achieved by high-performance liquid chromatography (HPLC) using a radial compression separation system equipped with a mu Porasil cartridge. The HPLC method applied allows the purification of 4 extracts/h. Recovery of 1,25(OH)2[3H]D3 after HPLC was 77 +/- 2.6% (mean +/- SD, n = 51). Since the recovery of 1,25(OH)2[3H]D3 was very reproducible, addition of labelled steroid to each single serum sample for monitoring recovery was omitted. The sensitivity of the assay was 0.8 pg/tube resulting in a detection limit of 3 ng/l, when 1 ml of serum was extracted. Intra-assay and inter-assay coefficients of variation were 12% and 16.8%, respectively. Serum 1,25(OH)2D3 concentration in 30 normal subjects (mean age: 25 yr) was 55 +/- 12 ng/l (mean +/- SD). In 55 elderly patients (mean age: 77 yr) the 1,25(OH)2D3 serum level was 32 +/- 12 ng/l (mean +/- SD) and in three patients with chronic renal failure on 1,25(OH)2D3 therapy 146 +/- 67 ng/l (mean +/- SD). Patients with chronic renal failure had reduced 1,25(OH)2D3 serum levels (mean 5.4 ng/l, range less than 3-11 ng/l, n = 10). In one patient with renal failure, following kidney transplantation the serum 1,25(OH)2D3 and creatinine levels were monitored from the 4th to the 12th post-surgical day: a highly significant negative correlation (r = 0.85) was found.

Problems regarding diagnosis and treatment of hormonally active and hormonally inactive parathyroid carcinomas arise from opposite sides, as is shown in two resp. cases. In functionally active tumors parathyroid origin is clear--but how to prove malignancy in early tumor stages? In inactive tumors malignancy is sound--but how to prove their parathyroid origin? Meticulous histologic examination (semithin-Layer) and cytophotometric DNA-measurement may be helpful diagnostic tools for active tumors, immunohistochemistry and analysis of parathormone fragments in plasma and tumor-cell-culture for inactive tumors. Nevertheless the surgeon's decision for radical surgery sometimes will have to be put on the intraoperative macroscopic situs--in order to provide curative treatment.

Fifteen patients with congestive heart failure (New York Heart Association III) were randomly assigned to treatment with either captopril or ramipril, a newly developed angiotensin converting enzyme inhibitor. Both groups were similar with respect to baseline hemodynamic measurements and plasma levels of norepinephrine, renin and vasopressin. The group receiving ramipril showed hemodynamic changes comparable to the group receiving captopril on the seventh day of treatment. The stroke volume index increased by 20% versus 21%, respectively, and the total peripheral resistance decreased by 13% versus 20%, respectively. The decrease in blood pressure and the tendency to decrease heart rate were similar in both groups. All patients had reactive hyperreninemia during therapy with the converting enzyme inhibitor. The resting elevated plasma norepinephrine decreased in both groups significantly, whereas vasopressin did not change. The hemodynamic improvement was more pronounced and comparable in both groups during exercise. Thus, ramipril is equally effective compared with captopril in the treatment of patients with severe congestive heart failure.

X-ray films of the hand skeleton (mammography technique), serum chemistry, and quantitative bone histology (micromorphometry of undecalcified sections, iliac crest spongiosa) were compared in 25 patients on maintenance hemodialysis. The X-ray findings correlated better with serum PTH levels than with bone histology. Of all radiological signs of renal osteodystrophy, pronounced subperiosteal resorption (radial aspect, second finger, middle phalanx) and periosteal new bone formation (middle phalanx) correlated best with histological indicators of osteitis fibrosa. These signs were never seen in control patients. Acroosteolysis (endphalanx) and intracortical or endosteal resorption (middle phalanx) were less specific (i.e., seen even in the absence of metabolic bone disease) and correlated less with bone histology. Osteosclerosis in iliac cancellous bone was paralleled by abnormal texture of spongy bone in the proximal metaphysis of the middle phalanx (second finger).

In 100 epileptic patients under treatment with long-term anti-convulsants, radiographs of the hands and feet, and estimations of serum 25-hydroxycholecalciferol, parathormone, alkaline phosphatase, calcium, and inorganic phosphate were done to detect a medication-induced osteomalacia. The correlation between the individual parameters was investigated. It was shown that the serum 25-hydroxycholecalciferol level and the skeletal radiograph were the most valuable in the early detection of osteomalacia. One of these investigations in addition to routine serum chemistry is recommended for the future at the yearly follow-up examinations of adult epileptics so that early and adequate treatment with vitamin D can be started.

Peptide hormones LH, FSH, TSH, e-peptide, prolactin, HCG, PTH, calcitonin and prostaglandin F2 alpha were evaluated in 25 patients with renal adenocancer. Prolactin elevation found in 45% was unrelated to the stage of the disease, while aberrant TSH and FSH were more sensitive in indicating distant metastasis. Prostaglandin F2 alpha, measured as a stable degradation product 13,14-DHK-PGF2 alpha, was frequently elevated and normalized following tumor nephrectomy within 12 month. Serum PTH was decreased in patients with tumor dissemination suggesting resorptive hypercalcemina, whereas none of the patient had circulating HCG levels. Therefore even patients without any paraneoplastic syndromes have a frequent change of peptide hormones directly or indirectly caused by renal cancer.

Case report of a female neonate with hypocalcemia and spasms. The cause was parathyroid insufficiency due to hyperparathroidism of the mother. The hypocalcemia was treated with a massive dose of Vitamin D; this led to a sharp rise of 25-OH-vitamin D levels in serum. The mother had kidney stones. There was hypercalcemia and a raised parathormone level. Diagnosis was confirmed by surgery. An adenoma weighing 7 g was removed.

Monoclonal antibodies against human thyroglobulin were produced by the hybridoma technique. Using three non-crossreactive monoclonal antibodies, an IRMA system was developed, with a polyclonal rabbit antibody fixed on microtiter plates as first extracting antibody. The monoclonal antibodies were used as second antibody, while anti-mouse IgG-biotin from goat and [125I]streptavidin served as the indicator system. The source of the monoclonal antibodies was diluted culture medium without purification. Sensitivities of 3-4 micrograms/l were obtained with all 3 monoclonal antibodies; interassay variation was about 5%. This test system will be used for further immunological characterization of circulating thyroglobulin in different thyroid diseases.

The potency and duration of a single dose of ranitidine and famotidine were compared in placebo-controlled studies. In addition, the effect of a single night-time dose of famotidine (40 mg) on gastric acid secretion and basal hormone levels was assessed before, during and after a 28-day treatment. Basal acid secretion was depressed by about 73% and 76% 12 hours after 300 mg ranitidine and 40 mg famotidine respectively. Pentagastrin-stimulated acid output was reduced by about 26% and 29%. 20 hours after both drugs, basal secretion was still inhibited by about 60%, whereas no effect on stimulated acid secretion could be detected. Nocturnal gastric acidity (23.00-07.00) was inhibited from 35.8 +/- 4.6 mmol/l to 1.8 +/- 0.5 mmol/l (94% inhibition) by 40 mg bedtime famotidine , and to 1.7 +/- 0.5 mmol/l (95% inhibition) by 300 mg ranitidine. Both drugs significantly reduced H+ concentrations during the following day. On day 29, i.e. 12 hours after the last famotidine dose, basal and stimulated acid secretion was reduced by some 50% and 26% respectively. On day 35, gastric acid output had returned to pretreatment values. Basal levels of prolactin, testosterone etc. were unchanged by 28-day famotidine treatment. Rantidine and famotidine may therefore be used as a single night-time dose in the acute treatment of peptic ulcer disease.

In a therapeutic trial 20 patients with femoral neck fractures (FNF) were treated alternatively without supplemental vitamin D, calcium and phosphate or with 15 000 I.U. vitamin D2, 500 mg Ca++ and 560 mg of phosphate daily. Within two weeks, 25-OH-D in serum increased in patients with supplementary therapy. It is concluded that in the German Federal Republic, vitamin D deficiency is frequently found in the elderly during the winter months and that vitamin D deficiency could be important for the development of FNF.

The status of vitamins A, B1, B2, B6, B12, C, D, and E as well as that of beta-carotene, biotin, and folate in the blood of over 500 epileptics was compared with that of a normal population. Male and female epileptics showed a poorer supply of vitamins B2, biotin, folate, and 25-hydroxycholecalciferol; the males, of only vitamin B6, B12, and E, and the women, of only vitamin A. Concentrations of beta-carotene and vitamin E in female epileptics were higher. The evaluation of relations between vitamin concentrations and mean daily dose, total dose of anticonvulsants, and duration of therapy suggested a possible influence of anticonvulsant medication on vitamins B1, B2, B6, C, D, E, beta-carotene, biotin, and folate. Concentrations of B vitamins as well as of folate were distinctly lower in patients under monotherapy with enzyme-inducing drugs than in those under valproate sodium. There was no relationship between bone mineral content and 25-hydroxycholecalciferol levels and between the neurographic parameters and the neurotropic vitamins of the B group, which also had no influence on concentration performance. Patients with poorer results in tests of the function of the central and the peripheral nervous system displayed a tendency towards lower vitamin-C levels. There were indications of potential links between immunological status and vitamin B6 and biotin. Males and females with a poorer supply of vitamin C, as well as males with lower riboflavin levels, showed a tendency towards macrocytic anaemia. Cerebellar disturbances were associated with lower concentrations of folate, of vitamin C or D, and possibly of biotin. The incidence of gingival hyperplasia could be linked to riboflavin, to biotin, and possibly also to vitamin C, D, or folate status.